This web page contains a list of genetic or inherited conditions which have been reported and lists the cat breeds affected. A brief description of the condition and references to published papers and sometimes abstracts are given. Mode of inheritance, where known, is given. Full lists of genetic and hereditary conditions affecting a particular breed can be found on the genetic conditions web page. Please note that these pages are intended for veterinary surgeons and that technical terminology is used throughout, with no translation for the lay person.

A similar database is available for genetic conditions of dogs from the University of Sydney.

To find the feline genetic or hereditary disease you are interested in, select from the list below, bearing in mind that it may be known by more than one name:

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

 

A

Amyloidosis

Alpha-mannosidosis

Anaemia - see pyruvate kinase deficiency

Ataxia - see Mucolipidosis II

Axonopathy- see distal axonopathy

Azotaemia

 

Amyloidosis (familial)

Abysinnian

Chew DJ, DiBartola SP, Boyce JT, et al. 1982. Renal amyloidosis in related Abyssinian cats. JAVMA 181 139

 

Alpha-mannosidosis

 

Clinical signs: progressively worsening neurological signs including tremors, loss of balance, and nystagmus from 4 to 18 weeks of age.

References


Vite CH, McGowan JC, Braund KG, Drobatz KJ, Glickson JD, Wolfe JH, Haskins ME. 2001 Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalities in the cat model of alpha-mannosidosis. J Neuropathol Exp Neurol. 60(8):817-28.

Alpha-mannosidosis is a disease caused by the deficient activity of alpha-mannosidase, a lysosomal hydrolase involved in the degradation of glycoproteins. The disease is characterized by the accumulation of mannose-rich oligosaccharides within lysosomes. The purpose of this study was to characterize the peripheral nervous system (PNS) and central nervous system (CNS) myelin abnormalities in cats from a breeding colony with a uniform mutation in the gene encoding alpha-mannosidase. Three affected cats and 3 normal cats from 2 litters were examined weekly from 4 to 18 wk of age. Progressively worsening neurological signs developed in affected cats that included tremors, loss of balance, and nystagmus. In the PNS, affected cats showed slow motor nerve conduction velocity and increased F-wave latency. Single nerve fiber teasing revealed significant demyelination/remyelination in affected cats. Mean G-ratios of nerves showed a significant increase in affected cats compared to normal cats. Magnetic resonance imaging of the CNS revealed diffuse white matter signal abnormalities throughout the brain of affected cats. Quantitative magnetization transfer imaging showed a 8%-16% decrease in the magnetization transfer ratio in brain white matter of affected cats compared to normal cats, consistent with myelin abnormalities. Histology confirmed myelin loss throughout the cerebrum and cerebellum. Thus, histology, electrodiagnostic testing, and magnetic resonance imaging identified significant myelination abnormalities in both the PNS and CNS that have not been described previously in alpha-mannosidosis.

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Azotaemia

Birman

 

Reference


Gunn-Moore DA, Dodkin SJ, Sparkes AH. 2002 An unexpectedly high prevalence of azotaemia in Birman cats. J Feline Med Surg. 4(3):165-6.

 

B

Blindness - see Mucolipidosis II and Progressive retinal atrophy

 

C

Cardiac defect - see cardiomyopathy, Mucolipidosis II; Myocardial disease; Patent Ductus Arteriosis and Ventricular Septal Defect

Cardiomyopathy - see Hypertrophic cardiomyopathy

Cataracts - see Chediak-Higashi syndrome

Cerebellar degeneration - hereditary

Chediak-Higashi syndrome

Christmas disease - see Haemophilia B

Coagulopathies

Congenital hypothyroidism

Congenital vestibular disease

Corneal clouding - see Mucopolysaccharidosis I.

Corneal sequestrum

Craniofacial malformation

Cutaneous asthenia - see Ehlers-Danlos syndrome.

 

Cerebellar degeneration - hereditary

Clinical signs: cerebellar dysfunction from the age of 7 to 8 weeks onward. Becomes progressively worse, but not fatal, between 1 and 2.5 months.

Mode of inheritance: autosomal recessive.


Inada S, Mochizuki M, Izumo S, Kuriyama M, Sakamoto H, Kawasaki Y, Osame M. 1996 Study of hereditary cerebellar degeneration in cats. Am J Vet Res. 57(3):296-301.

OBJECTIVE--To elucidate the nature of ataxia observed in 3 cats spanning 2 generations. DESIGN--Experimental breeding was attempted to confirm heritability of the disease and establish the mode of inheritance; the original 3 cats and their offspring were studied. ANIMALS--Seven diseased cats spanning 3 generations and 11 neurologically normal cats. PROCEDURE--Cats were examined by use of the following methods: clinical observation, hematologic and serum biochemical examinations, neurologic examination, electrodiagnostics, magnetic resonance imaging, lysosomal enzyme activity assay, horizontal transmission test, and virologic and pathologic examinations. RESULTS--All kittens (1 male and 3 females) obtained by backcrosses developed pure cerebellar dysfunction from the age of 7 to 8 weeks onward. It became progressively worse, but not fatal, between 1 and 2.5 months. Prenatal or perinatal infection with feline panleukopenia virus, inherited lysosomal storage diseases, including gangliosidosis and mannosidosis, and feline hereditary neuroaxonal dystrophy were excluded. Magnetic resonance imaging indicated that size of the cerebellum of diseased cats was markedly reduced. Cerebellar cortical degeneration, especially with extensive destruction of Purkinje cells, was observed microscopically. CONCLUSION--The disease was concluded to be cerebellar degeneration of a new clinical form in cats having an autosomal recessive mode of inheritance. CLINICAL RELEVANCE--When cerebellar dysfunction is diagnosed in a cat, hereditary cerebellar degeneration of this type should be considered in the differential diagnosis.

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Chediak-Higashi syndrome

Smoke blue Persians

Clinical signs: cataracts, nystagmus

 

References:

Collier LL, Bryan GM, Prieur DJ. 1979. Ocular manifestations of the Chediak-Higashi syndrome in four species of animals. JAVMA 175 587-590

Ocular examinations were performed on cattle, cats, mink, and mice affected with Chediak-Higashi syndrome (CHS). Bovine eyes were examined grossly and with an indirect ophthalmoscope, and Schirmer tear tests were performed. Feline eyes were examined grossly as well as with an indirect opthalmoscope and a slit lamp biomicroscope, and Schirmer tear tests were done on them. Postrotatory nystagmus was induced and measured in clinically normal Siamese cats, in clinically normal Persian and domestic short-haired cats, and in cats with CHS. Mink and mouse eyes were examined grossly with focal illumination. The animals with CHS had photophobia, pale irises, and fundic hypopigmentation associated with red fundic light reflections. Cats with CHS also had cataracts. Spontaneous nystagmus was observed in four of nine cats with CHS, and the duration of induced nystagmus was longer in the cats with CHS and in Siamese cats than in clinically normal cats that were not Siamese. Tear secretion appeared to be normal in all species of animals with CHS. The ocular manifestations of CHS in these animals were compared with those reported in man and were found to be similar.


Collier LC, King EJ, Prieur DJ. 1985 Tapetal degeneration in cats with Chediak-Higashi syndrome. Curr. Eye Res. 4 767-733

Kramer JW, Davis WC, Prieru DJ. 1977 The Chediak-Higashi syndrome of cats. Lab. Invest. 36 554-562

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Coagulopathies - see also Hageman (coagulation factor XII) deficiency

Devon Rex

 

Vitamin K-dependent multifactor coagulopathy

Devon Rex

 

Clinical signs: haemorrhage, prolonged clotting times, response to Vitamin K.

 

References:

Evans RJ. 1985 The blood and haemopoietic system. In Feline Medicine and Therapeutics. (Ed.) Chandler EA, Hilbery ADR, Gaskell CJ. 129-130

 

Littlewood JD, Shaw SC, Coombes LM.Vitamin K-dependent coagulopathy in a British Devon rex cat.J Small Anim Pract. 1995 Mar;36(3):115-8.Animal Health Trust, Newmarket, Suffolk.

Deficiencies of the vitamin K-dependent coagulation factors were identified in a Devon rex cat which had bled after castration. Haemorrhage was controlled by plasma transfusion. Clotting times were normalised by oral administration of vitamin K. This report confirms the existence of this bleeding disorder in a Devon rex cat in the United Kingdom.

 

Maddison JE, Watson AD, Eade IG, Exner T.1990 Vitamin K-dependent multifactor coagulopathy in Devon Rex cats. J Am Vet Med Assoc. 197(11):1495-7. Department of Veterinary Clinical Sciences, University of Sydney, N.S.W., Australia.

A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder.

 

Soute BA, Ulrich MM, Watson AD, Maddison JE, Ebberink RH, Vermeer C. 1992 Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats.Thromb Haemost. 68(5):521-5. Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.

Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to gamma-glutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.

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Congenital hypothyroidism

Abysinnian

Jones BR, Gruffydd-Jones TJ, Sparkes AH. 1991 Congenital hypothyroidism in the cat. FAB Bulletin 28 1 12

 

Congenital vestibular disease

Birmans, British Cream, Burmese, Persian, Siamese

 

Chrisman CL. 1980 Vet. Clin. N. Amer. 10 103

deLahunta A. 1977 Veterinary Neuroanatomy and Clinical Neurology. WB Saunders, Philadelphia 22

Evans RJ. 1985 The nervous system. In Feline Medicine and Therapeutics. (Ed.) Chandler EA, Hilbery ADR, Gaskell CJ. 54

 

Corneal sequestrum

Persian


Featherstone HJ, Sansom J.2004 Feline corneal sequestra: a review of 64 cases (80 eyes) from 1993 to 2000.Vet Ophthalmol. 2004 Jul-Aug;7(4):213-27.

Davies White Veterinary Specialists, Manor Farm Business Park, Higham Gobion SG3 5HR, UK. hjf@vetspecialists.co.uk

Feline corneal sequestrum is a common condition of the feline cornea. The purpose of this study was to provide a detailed description of the clinical features of the condition including the response to different management options and to assess the rate of recurrence. The medical records of 64 cases (80 eyes) of feline corneal sequestra that presented to the Animal Health Trust from 1993 to 2000 were reviewed. Fifty-two cases were reviewed retrospectively; 12 cases were assessed prospectively between April and September 2000 as part of a separate study. The Persian was the most frequently encountered breed and the mean age of affected cats was 5.6 years. At initial presentation, sequestra were unilateral in 58 cats and bilateral in 6 cats, 5 of which were Persians. Ocular discomfort and ocular discharge were common presenting signs, occurring in 42 and 36 eyes, respectively. Seventy-four eyes were managed surgically with keratectomy only (n = 44) or keratectomy followed by a graft procedure (n = 30). Sequestra recurred in 16 eyes in the study. There was no significant difference in the rate of recurrence between eyes that received a graft procedure (n = 5) and eyes that did not (n = 11) (P = 0.56). Complications following transection of conjunctival pedicle grafts were observed. Brown to black discoloration of noncorneal tissue and therapeutic biomaterials was observed, including discoloration of both viable and apparently nonviable grafted conjunctival tissue, small intestinal submucosa graft material and bandage contact lenses.

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Craniofacial malformation - see also mucolipidosis II

Burmese kittens

The cranial cavity is enlarged, cerebral hemispheres duplicated, eyes missing or small, there may be no nostrils or naval cavities.

Anon. 1982. Craniofacial malformation in Burmese kittens. Feline Practice. 12 6 32-33

 

D

Deafness

Dermatosparaxis - see Ehlers-Danlos syndrome

Diabetes mellitus

Diaphragmatic hernia

Distal axonopathy

Dwarfism

Dystocia

 

Deafness in white cats

See article on heredity of this by Roy Robinson.

 

Diabetes mellitus - type 2

Burmese, domestic


Rand J. 1999 Current understanding of feline diabetes: part 1, pathogenesis.J Feline Med Surg. 1(3):143-53.

Type-1 diabetes, resulting from immune-mediated destruction of beta cells, appears to be rare in cats. Type-2 diabetes, characterised by inadequate insulin secretion and impaired insulin action, is the most common form of diabetes in cats. Other specific forms of diabetes constitute a substantial minority of cases. The most common is pancreatic destruction from pancreatic adenocarcinoma. Less frequent causes are insulin resistance from other endocrinopathies including acromegaly. Diabetes in cats is characterised by variable loss of insulin secretory capacity and insulin resistance. Glucose toxicity, islet amyloid-deposition, and pancreatitis contribute to further loss of beta cells and failure of insulin secretion. A significant number of cats undergo remission of their diabetes, usually 1-3 months after good glycaemic control is instituted. Obesity, old age, and Burmese breed are recognised risk factors for the development of diabetes in cats.


Rand JS, Fleeman LM, Farrow HA, Appleton DJ, Lederer R. 2004 Canine and feline diabetes mellitus: nature or nurture? J Nutr. 134(8 Suppl):2072S-2080S.

There is evidence for the role of genetic and environmental factors in feline and canine diabetes. Type 2 diabetes is the most common form of diabetes in cats. Evidence for genetic factors in feline diabetes includes the overrepresentation of Burmese cats with diabetes. Environmental risk factors in domestic or Burmese cats include advancing age, obesity, male gender, neutering, drug treatment, physical inactivity, and indoor confinement. High-carbohydrate diets increase blood glucose and insulin levels and may predispose cats to obesity and diabetes. Low-carbohydrate, high-protein diets may help prevent diabetes in cats at risk such as obese cats or lean cats with underlying low insulin sensitivity. Evidence exists for a genetic basis and altered immune response in the pathogenesis of canine diabetes. Seasonal effects on the incidence of diagnosis indicate that there are environmental influences on disease progression. At least 50% of diabetic dogs have type 1 diabetes based on present evidence of immune destruction of beta-cells. Epidemiological factors closely match those of the latent autoimmune diabetes of adults form of human type 1 diabetes. Extensive pancreatic damage, likely from chronic pancreatitis, causes approximately 28% of canine diabetes cases. Environmental factors such as feeding of high-fat diets are potentially associated with pancreatitis and likely play a role in the development of pancreatitis in diabetic dogs. There are no published data showing that overt type 2 diabetes occurs in dogs or that obesity is a risk factor for canine diabetes. Diabetes diagnosed in a bitch during either pregnancy or diestrus is comparable to human gestational diabetes.

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Diaphragmatic hernia - see Ehlers Danlos

Most diaphragmatic hernias are traumatic in origin (usually post road accident).

 

References


Stork CK, Hamaide AJ, Schwedes C, Clercx CM, Snaps FR, Balligand MH. 2003 Hemiurothorax following diaphragmatic hernia and kidney prolapse in a cat.J Feline Med Surg. 5(2):91-6

A 3-year-old cat was presented with increasing dyspnoea over the past four days. Unilateral pleural effusion was diagnosed and a modified transudate was drained several times. Surgical exploration revealed intra-thoracic prolapse of the left kidney and partial herniation of the spleen through a dorsal, circumferential diaphragmatic tear. Biochemical analysis of the pleural fluid confirmed urothorax. Due to excessive fibrin deposit on the well-vascularised kidney it was impossible to re-establish left urinary pathways. Left-sided nephrectomy and diaphragmatic herniorrhaphy were performed. Postoperative recovery was uneventful and complete. This is the first report of an urothorax in veterinary medical literature.

 

White JD, Tisdall PL, Norris JM, Malik R. 2003 Diaphragmatic hernia in a cat mimicking a pulmonary mass. J Feline Med Surg. (3):197-201.

A seven-year-old castrated British shorthair cross cat was presented for coughing of five-weeks duration. Thoracic radiographs and an unguided bronchoalveolar lavage showed changes consistent with inflammatory airway disease. In addition, a soft tissue density was evident in the thoracic films between the heart and the diaphragm. Exploratory thoracotomy demonstrated a diaphragmatic hernia, probably congenital in origin, with incarceration of a portion of the hepatic parenchyma. The herniated portion of liver was resected surgically and the defect in the diaphragm closed. The cat was given a 10-day course of doxycycline post-operatively and the cough did not recur subsequently. In retrospect, the hernia was potentially an incidental problem, the cat's coughing being attributable to inflammatory airway disease.

 

Distal axonopathy

Birman.

Kittens of 8 to 10 weeks of age with slowly progressive posterior ataxia.

 

References:


Moreau PM, Vallat JM, Hugon J, Leboutet MJ, Vandevelde M. 1991 Peripheral and central distal axonopathy of suspected inherited origin in Birman cats.Acta Neu ropathol (Berl). 82(2):143-6.

Three female cats, littermates born from clinically normal parents, were examined at 8 to 10 weeks of age because of a slowly progressive posterior ataxia. Another cat from a previous litter from the same parents suffered from similar neurological symptoms. Histopathological examination of the nervous tissues of these animals revealed degeneration of axons and myelinopathy in a distal distribution pattern. Both peripheral nerves and central nervous system were involved. The central nervous system lesions were most prominent in the lateral pyramidal tracts of the spinal cord, the fasciculi gracili of the dorsal column in the cervical spinal cord and the cerebellar vermian white matter. In the PNS numerous degenerating nerve fibers were found in the sciatic nerves but not in the spinal nerve roots. Our findings show that these cats were suffering from a hereditary multisystem degeneration with a distribution pattern of the lesions suggestive of a distal axonopathy.

 

Dwarfism

Domestic, Siamese

Associated with lysosomal storage disease of the liver, these cats die between 1 and 4 months of age. See also gangliosidosis, Mucopolysaccharidosis, Mucopolysaccharidosis VI. Uneven litter sizes have been reported in cats infected with feline coronavirus.

Hegreberg GA, Norby DE. 1973. An inherited storage disease of cats. Fed. Proc. 32 821

Hegreberg GA, Norby DE, Hamilton MJ. 1974. Lysosomal enzyme changes in an inherited dwarfism of cats. Fed Proc. 33 598.

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Dystocia

Devon Rex, Persian and Siamese-type


Gunn-Moore
DA, Thrusfield MV. 1995 Feline dystocia: prevalence, and association with cranial conformation and breed.Vet Rec. 136(14):350-3.

The litter prevalence of feline dystocia was investigated using a questionnaire survey of cat breeders. Information was obtained on 2928 litters, from 735 queens. Dystocia was reported to have occurred in 5.8 per cent of litters. The level of dystocia in individual breeds ranged from 0.4 per cent of litters born in a large colony of cats of mixed breeding, to 18.2 per cent of litters in the Devon rex. Pedigree litters were at significantly higher risk than litters of cats of mixed breeding (odds ratio: 22.6). Relatively high levels of dystocia were identified in Siamese-type, Persian and Devon rex litters, whereas cats of mixed breeding showed a relatively low litter prevalence. Dolicocephalic and brachycephalic types were found to have significantly higher levels of dystocia than mesocephalic cats.

 

E

Ehlers-Danlos Syndrome

Encephalomyelopathy

 

Ehlers-Danlos Syndrome

Cutaneous asthenia is a connective tissue disease primarily of dogs and cats, resembling Ehlers-Danlos syndrome in man. It has also been reported in a rabbit. The skin is hyperextensible, thin, and fragile.

No breed predilection recorded so far.

 

References

 

Benitah N, Matousek JL, Barnes RF, Lichtensteiger CA, Campbell KL. 2004 Diaphragmatic and perineal hernias associated with cutaneous asthenia in a cat. J Am Vet Med Assoc. Mar 1;224(5):706-9, 698.

An 11-year-old cat was evaluated because of dyspnea. Since 11 months of age, the cat had hyperextensibility of the skin consistent with cutaneous asthenia. Radiographic examination revealed a diaphragmatic hernia with intestinal loops in the thorax. Electron microscopic examination of skin specimens revealed collagen fibers of highly variable diameter, consistent with cutaneous asthenia. The diaphragmatic hernia was surgically repaired and healed well. Four weeks later, a left-sided perineal hernia was repaired surgically, and 4 months later, a right-sided perineal hernia was repaired surgically and colopexy and cystopexy were performed. All surgical procedures were successful and tissues healed well. Dermatosparaxis is a rare hereditary disorder that commonly results in cutaneous fragility and hyperextensibility in affected animals. The diagnosis depends on clinical findings and light and electron microscopic changes in affected tissues. Surgical repair can be performed successfully in an affected cat, and healing of incisions can occur without complications.

 


Freeman LJ, Hegreberg GA, Robinette JD, Kimbrell JT. 1989 Biomechanical properties of skin and wounds in Ehlers-Danlos syndrome.Vet Surg. 8(2):97-102.

The biomechanical properties of wounded and nonwounded skin were studied in three dogs and three cats affected with type I Ehlers-Danlos syndrome. Three nonaffected dogs and one nonaffected cat served as controls. Samples of wounded skin and adjacent normal skin were harvested at days 75, 138, 141, 144, 147, and 150. Samples were subjected to uniaxial tensile strength testing. Tensile strength, energy absorbed, and site of failure were recorded. In the dogs with Ehlers-Danlos syndrome, there was an increase in tensile strength in samples containing a scar over adjacent intact skin. In nonaffected dogs, affected cats and the nonaffected cat, the nonwounded skin samples had greater tensile strength. The energy absorbed by the skin samples during testing was highly correlated with tensile strength.


Freeman LJ, Hegreberg GA, Robinette JD. 1989 Cutaneous wound healing in Ehlers-Danlos syndrome.Vet Surg. 18(2):88-96.

Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs, affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had dehiscence of all or part of the incision line and healed by granulation, contraction, and epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to determine if there were any differences in rates of healing between affected and nonaffected animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75, incision sites were recognized by fine, more compact collagen bundles and lack of adnexal structures, as compared with the adjacent dermis in both affected and nonaffected animals. Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals.

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Encephalomyelopathy

Birman

Onset 2-5 months of age. Hindlimb paresis and ataxia, which progresses to paralysis. Bilateral nuclear cataracts may be present. Condition is inherited. Histopathology: spongy changes, vacuolation and wallerian degeneration, mainly in thoracolumbar spinal cord. Diffuse lesions also present in brain. No treatment.

 

F

Facial dysmorphia - see Mucolipidosis II

Factor (coagulation) VIII deficiency - see Hemophilia A

Factor (coagulation) IX deficiency - see Haemophilia B

Factor (coagulation) XII deficiency - see Hageman

Familial hyperlipaemia

Feline infectious peritonitis - predisposition to development of

Feline leukocyte antigen restricted polymorphism

Flat-chested kittens

 

Familial hyperlipaemia

Siamese

 

Feline infectious peritonitis - predisposition to development of

Abyssinians, Australian Mist (more prone to effusive FIP), Bengals, Birmans, British Shorthair, Cornish Rex, Himalayans, Ragdolls and Rexes are MORE at risk

Domestic (aka European) short and longhairs (also known as moggy or mongrel cats), Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats are NOT AT INCREASED risk for development of FIP.

Burmese: in one study more at risk, in another study less at risk. In the former, Burmese were more prone to non-effusive FIP (Norris et al, 2005).

 

Susceptibility to FIP may have a polygenic hereditary component:  Drs Foley and Pedersen (1996) found that within the same breeding catteries, kittens from certain stud cats were more likely to develop FIP than kittens from other stud cats.

A very small percentage of cats is resistant to FCoV infection and FIP, but the mechanism is unknown.

One gets the impression that certain breeds crop up more often, as suffering from FIP, but that has to be weighed against the popularity of the breed in question – obviously the most popular breeds will tend to show up most often in the veterinary surgery.   This question was examined scientifically by Dr Pesteanu-Somogyi et al: Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes had a significantly higher risk of developing FIP, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats were not at increased risk for development of FIP. 

Norris et al (2005) found that the Australian Mist, Burmese, British Shorthair and Cornish Rex were more likely to present with FIP, while the Domestic Shorthair and Persian were under-represented.  They also noticed that the Australian Mist was more likely to develop effusive (wet) FIP while the Burmese was more likely to develop non-effusive (dry) FIP. 

 

References & further reading

Addie DD, Kennedy LJ, Ryvar R, Willoughby K, Gaskell RM, Ollier WE, Nart P, Radford AD. 2004 Feline leucocyte antigen class II polymorphism and susceptibility to feline infectious peritonitis.  J Feline Med Surg.  6(2):59-62.

Foley JE, Pedersen NC.  1996  The inheritance of susceptibility to feline infectious peritonitis in purebred catteries.  Feline Practice.  24  1  14-22

Norris JM, Bosward KL, White JD, Baral RM, Catt MJ, Malik R.  2005  Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990 – 2002).  Australian Veterinary Journal  83  11  666-673


Pesteanu-Somogyi LD, Radzai C, Pressler BM. 2005 Prevalence of feline infectious peritonitis in specific cat breeds. J Feline Med Surg.


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Feline leukocyte antigen DRB restricted polymorphism

Burmese

Reference


Kennedy LJ, Ryvar R, Brown JJ, Ollier WE, Radford AD. 2003 Resolution of complex feline leukocyte antigen DRB loci by reference strand-mediated conformational analysis (RSCA). Tissue Antigens. 62(4):313-23.

The DRB genes of the domestic cat are highly polymorphic. Studies based on clonal sequence analysis have suggested the existence of two distinct loci within individual animals and good evidence for 24 distinct FLA-DRB alleles. This variability, the complexity of clonal sequence analysis and its susceptibility to PCR-induced artefacts has represented a bottleneck to further progress. In this study we have applied reference strand-mediated conformational analysis (RSCA) to FLA-DRB. This protocol has been shown to be highly reproducible. Using five reference strands including two derived from non-domestic felines, we could distinguish 23 FLA-DRB alleles. We used RSCA to explore genetic polymorphism of FLA-DRB in 71 cats including 31 for which clonal sequence analysis was also available. On average, RSCA identified 0.9 more alleles within cats than clonal sequence analysis. Reference strand-mediated conformational analysis was also able to identify animals containing new alleles that could be targeted for sequence analysis. Analysis of allele patterns showed clear evidence for different allele distributions between breeds of cats, and suggested the Burmese breed may have highly restricted FLA-DRB polymorphism. Results from two families provided clear evidence for variation in the number of DRB genes on different haplotypes, with some haplotypes carrying two genes and some containing three. This study highlights the utility of RSCA for the resolution of complex amplicons containing up to six distinct alleles. A simple, rapid method for characterizing FLA-DRB makes possible studies on vaccine response and susceptibility/resistance to viral infections, which are a significant clinical problem in cats.

 

Flat-chested kittens

Burmese

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G

 

Gastric adenocarcinoma

Gastritis - chronic

Gangliosidosis

Gingivitis - hyperplastic, early onset

Glaucoma

Glycogen storage diseases

 

Chronic gastritis and gastric adenocarcinoma  

Persian

Clinical signs: vomiting, hematemesis, intermittent melena, and weight loss

Reference

Dennis MM, Bennett N, Ehrhart EJ.  2006  Gastric adenocarcinoma and chronic gastritis in two related Persian cats.  Vet Pathol.  43(3):358-62

 

Gangliosidosis

Domestic shorthair, Korat

Clinical signs: slowly progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Circulating monocytes and lymphocytes showed the presence of single or multiple empty vacuoles.

Mode of inheritance: autosomal, recessively inherited.

 

GM1 gangliosidosis

References


Cox NR, Morrison NE, Sartin JL, Buonomo FC, Steele B, Baker HJ. 1999 Alterations in the growth hormone/insulin-like growth factor I pathways in feline GM1 gangliosidosis.Endocrinology. 140(12):5698-704.

Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between thymocyte surface GM1 and thymic apoptosis in vivo, suggesting that other factors may be important to the pathogenesis of thymic involution in affected cats. Because GH and insulin-like growth factor I (IGF-I) are important hormonal peptides supporting thymic function and affecting growth throughout the body, particularly in the prepubescent period, several components of the GH/IGF-I pathway were compared in GM1 mutant and normal age-matched cats. GM1 mutant cat serum IGF-I concentrations were reduced significantly compared with those in normal cats by 150 days of age, and GM1 mutant cats had no peripubertal increase in serum IGF-I. Additionally, IGF-binding protein-3 was reduced, and IGF-binding protein-2 was elevated significantly in GM1 mutant cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary GH messenger RNA both were reduced significantly in GM1 mutant cats. After stimulation by exogenous recombinant canine GH, serum IGF-I levels increased significantly in GM1 mutant cats, indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that alterations are external to the liver.

 


De Maria R, Divari S, Bo S, Sonnio S, Lotti D, Capucchio MT, Castagnaro M. 1998 Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis.Acta Neuropathol (Berl). 96(3):307-14.

A 7-month-old Korat cat was referred for a slowly progressive neurological disease. Circulating monocytes and lymphocytes showed the presence of single or multiple empty vacuoles and blood leukocytes enzyme assay revealed a very low beta-galactosidase activity level (4.7 nmol/mg per h) as compared to unaffected parents and relatives. Histologically, the cat, euthanized at the owner request at 21 months of age, presented diffuse vacuolization and enlargement of neurons throughout the brain, spinal cord and peripheral ganglia, severe cerebellar neuronal cell loss, and moderate astrocytosis. Stored material was stained with periodic acid-Schiff on frozen sections and with the lectins Ricinus conmmunis agglutinin-I, concanavalin A and wheat germ agglutinin on paraffin-embedded sections. Ultrastructurally, neuronal vacuoles were filled with concentrically whorled lamellae and small membrane-bound vesicles. In the affected cat, beta-galactosidase activity was markedly reduced in brain (18.9%) and liver (33.25%), while total beta-hexosaminidase activity showed a remarkable increase. Quantitation of total gangliosides revealed a 3-fold increase in brain and 1.7-fold in liver of affected cat. High-performance thin layer chromatography (HPTLC) detected a striking increase of GM1-ganglioside. On densitometric analysis of HPTLC bands, the absorption of GM1-ganglioside band was 98.52% of all stained bands (GD1a, GD1b, GT1b). Based on clinical onset, morphological and histochemical features, and biochemical findings, the Korat cat GM1-gangliosidosis is comparable with the human type II (juvenile) form. However, clinical progression, survival time and level of beta-galactosidase deficiency do not completely fit with those of human type II GM1-gangliosidosis. The disease in the Korat cat is also different from other reported forms of feline GM1-gangliosidosis.

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Steiss JE, Baker HJ, Braund KG, Cox NR, Wright JC.1997 Profile of electrodiagnostic abnormalities in cats with GM1 gangliosidosis.Am J Vet Res. 58(7):706-9.

OBJECTIVE: To determine which electrodiagnostic tests yield abnormal findings in cats with GM1 gangliosidosis, and to determine the approximate age of onset of electrodiagnostic abnormalities. ANIMALS: Cats (28 to 335 days old) affected with GM1 gangliosidosis (n = 11) and unaffected controls (n = 14). PROCEDURE: Cats were grouped by age: group 1, < or = 90 days, group 2, 91 to 200 days; and group 3, > 200 days. Electrodiagnostic tests were conducted, including needle electromyography, motor and sensory nerve conduction velocity, spinal evoked potentials, and brainstem auditory evoked potentials. Results for control and affected cats were compared, using the general linear model for ANOVA and Scheffe's test for multiple comparisons. RESULTS: Needle electromyography did not reveal abnormal spontaneous activity in skeletal muscles of any cat; furthermore, statistical analysis did not indicate significant difference between affected and control groups for nerve conduction velocity, confirming that degeneration of peripheral nerve fibers is not a feature of this disease. However, spinal evoked potentials were abnormal in group-3 cats; conduction velocity within sensory pathways in the cranial part of the spinal cord was significantly slower in GM1-affected cats (P = 0.0002). Brainstem auditory evoked responses also were abnormal: wave V (generated in the region of the pons) had prolonged latency in cats of groups 2 and 3 (P = 0.0003 and 0.0001, respectively, at 90 decibels sound pressure level). In the oldest cats, latencies for earlier waves within the auditory pathway also were prolonged; wave I (generated by the cochlear nerve) was prolonged in group-3 cats (P = 0.0423). CONCLUSIONS: Motor and sensory nerve conduction velocities remained within normal limits in GM1-affected cats. However, spinal evoked potentials indicated slowing in conduction velocity along the cranial part of the spinal cord in group 3 cats. Brainstem auditory evoked responses indicated prolonged latencies in cats of groups 2 and 3.

 

GM2 gangliosidosis


Martin DR, Krum BK, Varadarajan GS, Hathcock TL, Smith BF, Baker HJ.2004 An inversion of 25 base pairs causes feline GM2 gangliosidosis variant.Exp Neurol. 187(1):30-7.

In G(M2) gangliosidosis variant 0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase (EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside and severe neurodegeneration. Distinct feline models of G(M2) gangliosidosis variant 0 have been described in both domestic shorthair and Korat cats. In this study, we determined that the causative mutation of G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair inversion at the extreme 3' end of the beta-subunit (HEXB) coding sequence, which introduces three amino acid substitutions at the carboxyl terminus of the protein and a translational stop that is eight amino acids premature. Cats homozygous for the 25-base-pair inversion express levels of beta-subunit mRNA approximately 190% of normal and protein levels only 10-20% of normal. Because the 25-base-pair inversion is similar to mutations in the terminal exon of human HEXB, the domestic shorthair cat should serve as an appropriate model to study the molecular pathogenesis of human G(M2) gangliosidosis variant 0 (Sandhoff disease).

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Muldoon LL, Neuwelt EA, Pagel MA, Weiss DL. 1994 Characterization of the molecular defect in a feline model for type II GM2-gangliosidosis (Sandhoff disease).Am J Pathol. 144(5):1109-18.

The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were produced from one normal and one affected animal, and cDNA clones homologous to human HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at position +39 of the putative coding region results in a frame shift and a stop codon at base +191. This disease-related deletion was consistently detected by sequencing of cloned polymerase chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and two additional affected animals. The defect was further demonstrated using single-strand conformational polymorphism analysis of the polymerase chain reaction products. In addition, alternative splicing of both normal and affected messenger RNAs was demonstrated. These results should facilitate the use of this animal model to assess gene therapy.

 


Yamato O, Matsunaga S, Takata K, Uetsuka K, Satoh H, Shoda T, Baba Y, Yasoshima A, Kato K, Takahashi K, Yamasaki M, Nakayama H, Doi K, Maede Y, Ogawa H.GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats.Vet Rec. 2004 Dec 4;155(23):739-44.
Erratum in: Vet Rec. 2005 Jan 15;156(3):86.

A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism developed neurological disorders, including ataxia, decreased postural responses and generalised body and head tremors, at between two and five months of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of G(M2)-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the activities of beta-hexosaminidases A and B in its leucocytes were markedly reduced. On the basis of these biochemical data, the cat was diagnosed antemortem with G(M2)-gangliosidosis variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at 10 months of age. Histopathologically, neurons throughout the central nervous system were distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these distended neurons. The compound which accumulated in the brain was identified as G(M2)-ganglioside, confirming G(M2)-gangliosidosis. A family study revealed that there were probable heterozygous carriers in which the activities of leucocyte beta-hexosaminidases A and B were less than half the normal value. The Sandhoff-like disease observed in this family of Japanese domestic cats is the first occurrence reported in Japan.

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Glaucoma

Burmese

References


Hampson EC, Smith RI, Bernays ME. 2002 Primary glaucoma in Burmese cats.Aust Vet J. 80(11):672-80.

OBJECTIVE: To document the clinical signs and management of primary glaucoma in Burmese cats. DESIGN: A retrospective study of six affected Burmese cats, from 1996 to 2001. Procedure Six Burmese cats diagnosed with primary glaucoma were managed over periods varying from 3 months to 4.5 years. Clinical details were obtained from practice records. Gonioscopic examination of the drainage or iridocorneal angle in eyes of these affected cats was made. RESULTS: Six desexed female Burmese cats (ages 7.0 to 10.5 years) presented with complaints of either unilateral (n = 4) or bilateral (n = 2) red eye, dilated pupil or enlarged eye. In one of the affected cats, one eye had been enucleated prior to the commencement of the study, thus a total of 11 eyes were examined. Clinically, all affected eyes (n = 8) had injected episcleral blood vessels and elevated intraocular pressure. Gonioscopy revealed the presence of nine narrow and two closed iridocorneal angles. Medical therapy included topical 2% dorzolamide (n = 8), 0.5% timolol maleate (n = 1), 0.005% latanoprost (n = 1) and 0.5-1.0% prednisolone acetate (n = 8). Surgery was performed in six eyes using either diode laser (n = 5) and/or cryothermy (n = 2) and one eye was eviscerated, with implantation of a prosthesis. With therapy, five affected eyes maintained vision and normal intraocular pressure, one eye remained blind with normal intraocular pressure, one eye remained blind with elevated intraocular pressure and one eye was eviscerated. CONCLUSIONS: The Burmese cat may be predisposed to primary narrow-angle glaucoma. Early diagnosis and continuous antiglaucoma therapy can help control intraocular pressure and maintain vision.

 

Gingivitis - hyperplastic, early-onset

Abysinnian, Persian

Clinical signs: hyperemic, proliferative gingivitis

 

Gingivitis-periodontitis - feline juvenile-onset

DSH, Maine Coon, Siamese

Small stature and have a history of being "sickly" as kittens, often with chronic upper respiratory disease. Initial oral signs occur just before eruption of adult teeth. Gingival recession, pocketing, bone loss and furcation exposures are common. Lesions may be localized or generalized and often first seen in the central lower incisor area.

Reference

Williams CA, Aller MS. 1992 Gingivitis/stomatitis in cats. Veterinary Clinics of North America. 22 6 1361 - 1383

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Glycogen storage diseases

Type IV glycogen storage disease

Norwegian Forest Cats

 

Reference


Fyfe JC, Giger U, Van Winkle TJ, Haskins ME, Steinberg SA, Wang P, Patterson DF.1992 Glycogen storage disease type IV: inherited deficiency of branching enzyme activity in cats.Pediatr Res.32(6):719-25.

Glycogen storage disease type IV due to branching enzyme deficiency was found in an inbred family of Norwegian forest cats, an uncommon breed of domestic cats. Skeletal muscle, heart, and CNS degeneration were clinically apparent and histologically evident in affected cats older than 5 mo of age, but cirrhosis and hepatic failure, hallmarks of the human disorder, were absent. Beginning at or before birth, affected cats accumulated an abnormal glycogen in many tissues that was determined by histochemical, enzymatic, and spectral analysis to be a poorly branched alpha-1,4-D-glucan. Branching enzyme activity was less than 0.1 of normal in liver and muscle of affected cats and partially deficient (0.17-0.75 of normal) in muscle and leukocytes of the parents of affected cats. These data and pedigree analysis indicate that branching enzyme deficiency is a simple autosomal recessive trait in this family. This is the first reported animal model of human glycogen storage disease type IV. A breeding colony derived from a relative of the affected cats has been established.

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H

Hemophilia A (factor VIII deficiency)

Haemophilia B - factor IX deficiency - Christmas disease

Hageman (coagulation factor XII) deficiency

Heart defect - see Ventricular Septal Defect

Heart disease - Hypertrophic cardiomyopathy, Mucolipidosis II; Myocardial disease; Patent Ductus Arteriosis and Ventricular Septal Defect

Hernia

Hip dysplasia

Hypokalaemic myopathy
 

Haemophilia B - factor IX deficiency - Christmas disease

British shorthair, Domestic

Clinical signs: regenerative anaemia, haemorrhage, subcutaneous haematomas, prolonged bleeding times, shifting lameness.

References

Dillon AR, Boudreaux MK. 1988 Combined factors IX and XII deficiencies in a family of cats.J Am Vet Med Assoc. 193(7):833-4.

Combined factors IX and XII deficiencies were detected in a family of cats in which 2 male kittens had bleeding diathesis. The combination of factors IX and XII deficiencies in one male kitten did not appear to exacerbate bleeding when compared with a sole deficiency of factor IX in its male sibling. Neutering of carrier females and affected males was recommended. Blood transfusions before castration of affected males was advised.


Goree M, Catalfamo JL, Aber S, Boudreaux MK. 2005 Characterization of the mutations causing hemophilia B in 2 domestic cats.J Vet Intern Med. 2005 Mar-Apr;19(2):200-4.

The purpose of the present study was to determine the normal sequence for the gene encoding factor IX in cats and to characterize the genetic basis for hemophilia B in 2 unrelated male, domestic, mixed-breed cats. Genomic DNA sequence for the entire coding region of the factor IX gene was determined in the affected cats and compared to the sequence obtained from a healthy cat. The factor IX gene in cats encodes a mature protein consisting of 420 amino acids, unlike genes in humans and dogs that encode 415 and 413 amino acid proteins, respectively. Affected cat 1 had a single nucleotide change in exon 8 at the 1st nucleotide position of the codon encoding an arginine (CGA to TGA) at amino acid position 338. This mutation would be predicted to result in the appearance of a premature stop codon in the portion of the gene encoding much of the catalytic domain of the protein. Affected cat 2 had a single nucleotide change in exon 4 at the 2nd nucleotide position of the codon encoding amino acid 82 (TGT to TAT), which would be predicted to result in the substitution of a tyrosine for a cysteine. This substitution would likely result in disruption of a disulfide bond crucial to normal protein structure and function. This study represents the 1st time hemophilia B has been characterized at the molecular level in cats.

 

Lutze G, Kutschmann K, Furst K, Schneppenheim R. 2005 Hemophilia B (factor IX deficiency) with concomitant factor XII degradation in a male crossbreed cat. Berl Munch Tierarztl Wochenschr. 118(5-6):255-60.

A male cat suffered from a severe haemorrhagic disorder manifesting as deep, partly infected cutaneous haematomas, enhanced and prolonged bleeding after injuries and subsequent lameness at several occasions. Bleeding resulted in severe anaemia with haematocrit falling to as low as 0.10 L/L. Haemophilia B was diagnosed based on factor IX deficiency with a functional residual activity of 5% and factor IX antigen of 8%, respectively. Additionally, factor XII activity was reduced to 32% of normal. The mutation 31217G==>A in exon 8 of the factor IX gene, predicting the amino acid exchange G366R was identified as the cause of moderate factor IX deficiency. This is the first mutation identified in cats with haemophilia B. Treatment was limited to local therapy and palliation, insufficient to prevent lethal outcome due to severe anaemia.

 

Maggio-Price L, Dodds WJ. 1993 Factor IX deficiency (hemophilia B) in a family of British shorthair cats.J Am Vet Med Assoc. 203(12):1702-4.

This report describes the clinical findings of a British shorthair cat with hemophilia B, the family pedigree surrounding the case, and how this disorder can be perpetuated in rare breeds of cats that may be inbred by necessity. Young cats with histories of bleeding episodes following elective or other surgical procedures, periodic shifting lamenesses, or the development of subcutaneous hematomas should be suspect for an inherited coagulation disorder. Hemophilia A (factor VIII deficiency) or hemophilia B (factor IX deficiency) are the most likely causes, although other inherited bleeding disorders also have been recognized in cats.


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Hageman (coagulation factor XII) deficiency

Domestic

Mode of inheritance: autosomal recessive

References

Dillon AR, Boudreaux MK. 1988 Combined factors IX and XII deficiencies in a family of cats.J Am Vet Med Assoc. 193(7):833-4.

Combined factors IX and XII deficiencies were detected in a family of cats in which 2 male kittens had bleeding diathesis. The combination of factors IX and XII deficiencies in one male kitten did not appear to exacerbate bleeding when compared with a sole deficiency of factor IX in its male sibling. Neutering of carrier females and affected males was recommended. Blood transfusions before castration of affected males was advised.


Kier AB, Bresnahan JF, White FJ, Wagner JE. The inheritance pattern of factor XII (Hageman) deficiency in domestic cats.Can J Comp Med. 1980 Jul;44(3):309-14.

Measurements of coagulation factor XII levels in F1 progeny of a cat having factor XII deficiency revealed an autosomal recessive pattern similar to that reported in humans (Hageman trait). A study of the pedigree of the colony revealed that F1 kittens had approximately 50% factor XII activity while kittens produced by backcrossing with an F1 progeny possessed an average of 50% and a less than 2% factor XII activity in an approximate 1:1 ratio. Kittens having an average of 50% factor XII activity were postulated heterozygous for the trait while progeny with less than 2% activity were considered genetically homozygous.

 

Hernia - hernias can be secondary to Ehlers-Danlos syndrome

Diaphragmatic hernia

Hiatus hernia

Perineal hernia

Umbillical hernia

 

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Hip dysplasia

Clinical signs: hindlimb lameness, history of constipation

 

References


Keller GG, Reed AL, Lattimer JC, Corley EA. 1999 Hip dysplasia: a feline population study.Vet Radiol Ultrasound. 40(5):460-4.

The study population consisted of cats presented to the University of Missouri-Columbia Veterinary Medical Teaching Hospital from January 1, 1991 through December 31, 1995. Ventrodorsal radiographs including the pelvic region were evaluated for radiographic evidence of hip dysplasia. Each radiograph was evaluated independently by three board-certified veterinary radiologists and a consensus normal of dysplastic evaluation was determined. There were 684 cats from 12 breeds. The data derived from this study indicate the frequency of feline hip dysplasia in this population to be about 6.6% (45/684) and that the incidence appears to be breed dependent. Also, the radiographic appearance of hip dysplasia in cats is different than in dogs. A shallow acetabulum with remodeling and proliferation involving the cranio-dorsal acetabular margin were the most common radiographic signs. Minimal remodeling of the femoral neck was seen.


Patsikas MN, Papazoglou LG, Komninou A, Dessiris AK, Tsimopoulos G. 1998 Hip dysplasia in the cat: a report of three cases. J Small Anim Pract. 39(6):290-4.

Hip dysplasia was diagnosed in three cats. Two were presented with a history of hindlimb lameness and the other had a history of constipation. All were confined for two weeks and showed considerable clinical improvement. At follow-up examination the cats were free of clinical signs despite the deterioration in the radiological appearance of their hips. Luxation or subluxation of the hips, insufficient development of the craniolateral acetabular edges, loss of the arched shape of the cranial subchondral acetabular bones, shallow acetabula and secondary degenerative changes on the femoral heads and necks were the main radiological findings in the affected cats.

Hypertrophic cardiomyopathy

Breeds: British Shorthair, Maine Coon, Ragdolls

Clinical signs: sudden death, thickened wall of left ventricle on echocardiography.

Ferasin (2009) provides best review of HCM this author has ever seen.

Mode of inheritance: autosomal dominant mode in Maine Coon and maybe also in British Shorthair and Ragdolls (Ferasin, 2009)

References

Ferasin L. 2009  Feline myocardial disease. 1: Classification, pathophysiology and clinical presentation.  J Feline Med Surg.  11(1):3-13.

Meurs KM, Sanchez X, David RM, Bowles NE, Towbin JA, Reiser PJ, Kittleson JA, Munro MJ, Dryburgh K, Macdonald KA, Kittleson MD.  2005 A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy.  Hum Mol Genet. 14(23):3587-93.

 

 

Hypokalaemic myopathy

Burmese

Clinical signs: periodic muscle weakness and cervical ventroflexion, onset can be as early as 10 weeks old.

Mode of inheritance: homozygote recessive

 

References

Gaschen F, Jaggy A, Jones B. 2004 Congenital diseases of feline muscle and neuromuscular junction. J Feline Med Surg. (6):355-66.

Although muscle diseases occur relatively rarely in cats, a number of congenital feline myopathies have been described over the last 20 years and are reviewed in this paper. Some of them have been reported exclusively in specific breeds, including the hypokalaemic myopathy of Burmese cats, type IV glycogen storage disease in Norwegian Forest cats, or the myopathy of Devon Rex. Other congenital disorders of muscle and neuromuscular junction such as myotonia congenita, dystrophin-deficient hypertrophic feline muscular dystrophy, laminin alpha2 deficiency, or congenital myasthenia gravis may occur in any cat. A systematic approach is essential in order to efficiently obtain a timely diagnosis in cats showing signs of muscle disease. After a thorough clinical examination, this approach includes blood analyses (eg, serum concentration of muscle enzymes), electrophysiology where available (electromyography, nerve conduction studies), and sampling of muscle biopsies for histological, histochemical and immunohistochemical evaluation. When available, detection of healthy carriers of these genetic disorders is important to eliminate the gene mutations from breeding families. Clinicians regularly receiving feline patients must have a good knowledge of congenital feline myopathies and the features which enable a diagnosis to be made and prognosis given. Besides preserving or restoring the well-being of the myopathic patient, rapid and efficient information and counselling of the breeders are of central importance in order to prevent the recurrence of the problem in specific breeding lines.

 

Jones BR, Swinney GW, Alley MR. 1988 Hypokalaemic myopathy in Burmese kittens.N Z Vet J. 36(3):150-1.

Since 1984 there have been a number of reports of polymyopathy in cats characterised by clinical signs of generalised weakness of the limb and neck muscles. In most of these cases the polymyopathy was associated with a concurrent hypokalaemia. A direct causal relationship was not established in one series of cases, but in the second excessive urine potassium loss with decreased potassium intake was suspected. It was concluded by these authors that increased urinary potassium secretion was a basic response to renal dysfunction in cats. Periodic muscle weakness has also been recognised in young Burmese kittens (10 weeks to one year) which was characterised by ventroflexion of the neck, elevated creatinine phosphokinase (CPK) activity and intermittent hypokalaemia.


Lantinga E, Kooistra HS, van Nes JJ. 1998 Periodic muscle weakness and cervical ventroflexion caused by hypokalemia in a Burmese cat. Tijdschr Diergeneeskd. 123(14-15):435-7.

A 2-year-old female Burmese cat was referred to the University Hospital of Companion Animals of Utrecht University because of periodic muscle weakness and cervical ventroflexion. Laboratory examinations revealed hypokalemia. The combination of breed, clinical signs and hypokalemia warranted the diagnosis of 'periodic hypokalemic myopathy', a homozygote recessive hereditary disease in Burmese cats. Potassium supplementation resulted in complete disappearance of the signs. Possible causes of hypokalemia in the cat are discussed.

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L

Laminin alpha2 deficiency - see muscular dystrophy

Lipoprotein lipase deficiency - congenital

 

Lysosomal storage disease

 

Lipoprotein lipase deficiency - congenital

Clinical signs: fasting hyperlipaemia, lipaemia retinalis, peripheral neuropathies and subcutaneous xanthomas

 

References


Johnstone AC, Jones BR, Thompson JC, Hancock WS. 1990 The pathology of an inherited hyperlipoproteinaemia of cats. J Comp Pathol. 102(2):125-37

The gross and histological features of congenital lipoprotein lipase deficiency are described in eight cats. The main histological features could be directly related to the presence of the chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques. Focal degenerative changes were, however, present within arteries and this may indicate blood vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises from pressure necrosis of adjacent xanthomata and alterations in renal blood flow.

 

Jones BR, Wallace A, Harding DR, Hancock WS, Campbell CH 1983.Occurrence of idiopathic, familial hyperchylomicronaemia in a cat. Vet Rec. 112(23):543-7.

Primary hyperlipoproteinaemia (hyperchylomicronaemia with slight very low density lipoprotein elevation) is described in two related male cats. Fasting hyperlipaemia, lipaemia retinalis and subcutaneous xanthomas were detected on clinical examination. In one cat lipoprotein lipase activity measured after heparin activation was significantly reduced compared to the response in a normal cat. The lipid and protein concentration in each of the lipoprotein classes and the lipoprotein distribution of the two hyperlipaemic cats, two normolipaemic relations and 16 normolipaemic adult cats were determined. Plasma cholesterol and triglyceride levels were elevated in the hyperlipaemic cats with the major proportion of triglyceride and cholesterol being present in chylomicrons whereas in normolipaemic cats the majority of triglyceride was contained in very low density lipoprotein. High density lipoprotein was the predominant lipid carrier in both the normolipaemic and the hyperlipaemic cats but the protein content in chylomicrons was elevated in the two affected cats. The lipoprotein distribution in normal cats in this study agrees with previously reported values. The hyperlipaemic cats showed many of the features of familial lipoprotein lipase deficiency (type I hyperlipoproteinaemia, exogenous chylomicronaemia) which is an inherited disease in man.

 

Jones BR, Johnstone AC, Cahill JI, Hancock WS. 1986 Peripheral neuropathy in cats with inherited primary hyperchylomicronaemia.Vet Rec. 1986 Sep 13;119(11):268-72.

Primary hyperlipoproteinaemia (hyperchylomicronaemia) with a slight increase in very low density lipoprotein) is described in 20 cats. Fasting hyperlipaemia, lipaemia retinalis and peripheral neuropathies were the most frequently detected clinical signs. The disease is thought to be inherited as an autosomal recessive trait but the exact mode of inheritance has not been determined. Affected cats showed reduced lipoprotein lipase activity measured after heparin activation compared with the response in normal cats. Plasma triglyceride and cholesterol were increased in all the cats with the major proportion of triglyceride and cholesterol being present in chylomicrons. The peripheral nerve lesions were caused by compression of nerves by lipid granulomata. It is probable that the lipid granulomata result from trauma because the nerves most often affected were at sites like the spinal foraminae where they were susceptible to trauma.


Thompson
JC, Johnstone AC, Jones BR, Hancock WS. 1989 The ultrastructural pathology of five lipoprotein lipase-deficient cats.J Comp Pathol. 101(3):251-62.

The ultrastructural pathology of cats suffering from familial lipoprotein lipase deficiency is described. There were large numbers of lipid vacuoles within hepatocytes, epithelial cells of the proximal convoluted tubule of kidney and macrophages of the liver, spleen and lymph node. The older cats tended to have larger quantities of ceroid within hepatocytes and macrophages, and all stages of development of ceroid were observed. Chylomicron emboli were seen within the glomerular capillaries and interlobular blood vessels. There was podocyte foot fusion and thickening of basement membranes of glomeruli, Bowman's capsule and some proximal convoluted tubules, similar to that seen in diabetes mellitus. These changes represent a non-specific reaction of the kidney to noxious insults such as hypoxia caused by emboli. Transformation of smooth muscle cells from a contractile to a synthetic state was seen in the splenic trabeculae and, to a lesser extent, in blood vessels. Dilatations of the nuclear membrane of the lymphocytes were noted, the significance of which is unknown.

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Lysosomal storage disease

See also alpha-mannosidosis and the mucopolysaccharidoses.

Hegreberg GA, Norby DE, Hamilton MJ. 1974. Lysosomal enzyme changes in an inherited dwarfism of cats. Fed Proc. 33 598.

 

M

Mannosidosis

Manx

Mucolipidosis type II

Mucopolysaccharidosis

Mucopolysaccharidosis I.

Mucopolysaccharidosis VI

Mucopolysaccharidosis VII

Muscular dystrophy

Myocardial disease

Myopathy

 

Mannosidosis

Vacuolation of lymphocytes and monocytes.

 

Manx


Robinson R. 1993 Expressivity of the Manx gene in cats. J Hered. 1993 May-Jun;84(3):170-2.

New genetic data are presented which indicate that the assortment data for the mutant Manx gene, M, does not depart from normal expectation and does not enjoy a selective advantage at some stage of gametogenesis, as has been hypothesized. The variable expression of Manx taillessness is a remarkable and consistent feature of the Manx syndrome, encompassing the posterior skeleton, neural organization, and growth of soft tissues. The expression is partly genetic in origin, and the heritability is estimated to be in the region of h2 = 0.40 +/- 0.11.

 

Mucolipidosis type II

Domestic

Clinical signs: clinical features in affected kittens were observed from birth in some kittens, others are months old when presented. Clinical signs include failure to thrive, abnormal facial features, retarded growth, behavioral dullness, facial dysmorphia, diffuse retinal degeneration leading to blindness by 4 months of age, ataxia, progressive hindlimb paresis, upper respiratory signs, cardiac failure. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion.

Mode of inheritance: autosomal recessive

 

References

Hubler M, Haskins ME, Arnold S, Kaser-Hotz B, Bosshard NU, Briner J, Spycher MA, Gitzelmann R, Sommerlade HJ, von Figura K. 1996 Mucolipidosis type II in a domestic shorthair cat. J Small Anim Pract. 1996 Sep;37(9):435-41.

A seven-month-old, female domestic shorthair cat was presented to the Veterinary Teaching Hospital, University of Zurich, with abnormal facial features, retarded growth and progressive hindlimb paresis. On physical examination the cat had a flat, broad face with hypertelorism, frontal bossing, small ears and thickened upper and lower eyelids. The corneas of both eyes were clear and the pupils were dilated. The skin was generally thickened, most prominently on the dorsal aspect of the neck. Radiography of the entire skeleton revealed a severely deformed spinal column, bilateral hip luxation with hip dysplasia, an abnormally shaped skull and generalised decreased bone opacity. The clinical features and radiographic changes were suggestive of mucopolysaccharidosis. The toluidine blue spot test on a urine sample, however, was negative for glycosaminoglycans. Further biochemical investigations revealed a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) in peripheral leukocytes and an elevation of many lysosomal enzymes in the serum of the cat which is diagnostic for mucolipidosis type II. Histology and electron microscopy of different tissues are briefly summarised. The findings of this cat, the first reported case of mucolipidosis type II are compared with other similar storage diseases described in the cat.

 

Mazrier H, Van Hoeven M, Wang P, Knox VW, Aguirre GD, Holt E, Wiemelt SP, Sleeper MM, Hubler M, Haskins ME, Giger U. 2003 Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease. J Hered. 94(5):363-73.

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage disease.

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Mucopolysaccharidosis

Siamese

The mucopolysaccharidoses (MPS) are inherited metabolic disorders resulting from the defective catabolism of glycosaminoglycans.


Cowell KR, Jezyk PF, Haskins ME, Patterson DF. 1976 Mucopolysaccharidosis in a cat. J Am Vet Med Assoc. 169(3):334-9.

A young adult female Siamese cat born of a mother-son mating was referred because of dwarfism, facial abnormalities, severe skeletal deformities, multifocal neurologic deficits, and retinal atrophy. Cats of similar appearance had been observed in a previous litter of the same parents. Metachromatic inclusion bodies were demonstrated in circulating leukocytes. The urine contained a high concentration of mucopolysaccharide, as detected by the toluidine blue spot test. The uronic acid content of the cetylpyridinium chloride-precipitable mucopolysaccharide in the urine was 17 times greater than that in the urine from a control cat of the same age and breed.


Mucopolysaccharidosis I.

 

Clinical signs: corneal clouding

Reference


Kakkis ED, Schuchman E, He X, Wan Q, Kania S, Wiemelt S, Hasson CW, O'Malley T, Weil MA, Aguirre GA, Brown DE, Haskins ME. 2001 Enzyme replacement therapy in feline mucopolysaccharidosis I. Mol Genet Metab. 72(3):199-208.

ekakkis@biomarinpharm.com

Enzyme replacement therapy (ERT) has long been considered an approach to treating lysosomal storage disorders caused by deficiency of lysosomal enzymes. ERT is currently used to treat Gaucher disease and is being developed for several lysosomal storage disorders now that recombinant sources of the enzymes have become available. We have continued development of ERT for mucopolysaccharidosis I (MPS I) using the feline model. Recombinant alpha-L-iduronidase was administered intravenously at low dose (approximately 0.1 mg/kg or 25,000 units/kg) to four cats and high dose (0.5 mg/kg or 125,000 units/kg) to two cats on a weekly basis for 3- or 6-month terms. Clinical examinations showed distinct clearing of corneal clouding in one cat although clinical effects in the others were not evident. Biochemical studies of the cats showed that the enzyme was distributed to a variety of tissues although the liver and spleen contained the highest enzyme activities. Glycosaminoglycan storage was decreased in liver and spleen, and the histologic appearance improved in liver, spleen, and renal cortex. Enzyme was not consistently detected in cerebral cortex, brainstem, or cerebellum and the histologic appearance and ganglioside profiles did not improve. A variety of other tissues showed low variable uptake of enzyme and no distinct improvement. IgG antibodies to alpha-L-iduronidase were observed in five cats with higher titers noted when higher doses were administered. Mild complement activation occurred in three cats. Enzyme replacement therapy was effective in reversing storage in some tissues at the biochemical and histologic level in MPS I cats but an improved tissue distribution and prevention of a significant immune response could make the therapy more effective.

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Mucopolysaccharidosis VI

Siamese

Clinical signs: dwarfism, degenerative joint disease, skeletal deformities, facial dysmorphia due to epiphyseal dysplasia,degenerative joint disease, corneal clouding, and abnormal leukocyte inclusions.

 

References and abstracts.


Crawley AC, Muntz FH, Haskins ME, Jones BR, Hopwood JJ. 2003 Prevalence of mucopolysaccharidosis type VI mutations in Siamese cats.J Vet Intern Med. 17(4):495-8.

allison.crawley@adelaide.edu.au

Mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease, is one of the more prevalent inherited diseases in cats and is commonly found in cats with Siamese ancestry. The prevalence of 2 known MPS VI mutations in cats was investigated in 101 clinically normal Siamese cats, in 2 cats with clinical signs of MPS VI, and in 202 cats from 4 research colonies. The mutation L476P which causes a severe clinical phenotype, was present on both alleles in the known MPS VI cats from Italy and North America and was present in all research colonies that originated from North America. However, LA76P was not detected in the Siamese population screened. In contrast, the mutation D520N, which causes a mild clinical phenotype, was identified in 23 of 202 (11.4%) alleles tested in Siamese cats from 3 continents, 2 of which were homozygous for D520N. Thus, the D520N mutation was widespread, and it is likely that cats inheriting both mutations (LA76P/D520N compound heterozygotes) would be in the general Siamese population, particularly in North America. Practitioners should note the high incidence of degenerative joint disease in these animals.


Crawley
AC, Yogalingam G, Muller VJ, Hopwood JJ. 1998 Two mutations within a feline mucopolysaccharidosis type VI colony cause three different clinical phenotypes. J Clin Invest. 101(1):109-19

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-4-sulfatase (4S). A feline MPS VI model used to demonstrate efficacy of enzyme replacement therapy is due to the homozygous presence of an L476P mutation in 4-sulfatase. An additional mutation, D520N, inherited independently from L476P and recently identified in the same family of cats, has resulted in three clinical phenotypes. L476P homozygotes exhibit dwarfism and facial dysmorphia due to epiphyseal dysplasia, abnormally low leukocyte 4S/betahexosaminidase ratios, dermatan sulfaturia, lysosomal inclusions in most tissues including chondrocytes, corneal clouding, degenerative joint disease, and abnormal leukocyte inclusions. Similarly, D520N/D520N and L476P/D520N cats have abnormally low leukocyte 4S/betahexosaminidase ratios, mild dermatan sulfaturia, lysosomal inclusions in some chondrocytes, and abnormal leukocyte inclusions. However, both have normal growth and appearance. In addition, L476P/D520N cats have a high incidence of degenerative joint disease. We conclude that L476P/D520N cats have a very mild MPS VI phenotype not previously described in MPS VI humans. The study of L476P/D520N and D520N/ D520N genotypes will improve understanding of genotype to phenotype correlations and the pathogenesis of skeletal dysplasia and joint disease in MPS VI, and will assist in development of therapies to prevent lysosomal storage in chondrocytes.


Ho TT, Maguire AM, Aguirre GD, Surace EM, Anand V, Zeng Y, Salvetti A, Hopwood JJ, Haskins ME, Bennett J. 2002 Phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI. J Gene Med. 4(6):613-21.

BACKGROUND: Mucopolysaccharidosis VI (MPS VI), due to recessively inherited 4-sulfatase (4S) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. Retinal involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine whether recombinant adeno-associated virus (AAV)-mediated delivery of 4S would reverse the RPE pathology seen in MPS VI cats. METHODS: AAV.f4S, containing the feline 4S cDNA, was delivered unilaterally to eyes of affected cats by subretinal or intravitreal injection. Contralateral eyes received AAV with the green fluorescent protein (GFP) reporter gene as control. At 2-11 months post-injection, the cats were sacrificed and the treatment effects were evaluated histologically. RESULTS: By ophthalmoscopy and histological analyses, GFP was evident as early as 4 weeks and persisted through the latest time point (11 months). Untreated and AAV.GFP-treated diseased retinas contained massively hypertrophied RPE cells secondary to accumulation of dilated lysosomal inclusions containing dermatan sulfate. MPS VI eyes treated subretinally with AAV.f4S had minimal RPE cell inclusions and, consequently, were not hypertrophied. CONCLUSIONS: AAV-mediated subretinal delivery of f4S provided correction of the disease phenotype in RPE cells of feline MPS VI, supporting the utility of AAV as a vector for the treatment of RPE-specific as well as lysosomal storage diseases.


Macri B
, Marino F, Mazzullo G, Trusso A, De Maria R, Amedeo S, Divari S, Castagnaro M. 2002 Mucopolysaccharidosis VI in a Siamese/short-haired European cat. J Vet Med A Physiol Pathol Clin Med. Oct;49(8):438-42.

A 3-year-old Siamese/short-haired European cat was referred for clinical disease characterized by dwarfism, facial dysmorphia, paralysis, small and curled ears, corneal clouding and large areas of alopecia. X-ray examination showed multiple bone dysplasia. On the basis of clinical features a form of mucopolysaccharidosis was suspected. The cat, killed at the owner's request, presented several severe skeletal deformities such as long caudal limbs, enlarged thorax with sunken breastbone, vertebral ankylosis in many spinal segments and visceral involvement. Histologically, the cat showed diffuse vacuolization and enlargement of cells in cartilage, bone and visceral organs. Ultrastructurally, membrane-bound vacuoles were filled with fibrillar and fluffy-material or concentrically whorled lamellae. Arylsulphatase B activity was 3.24 nm/mg/h in the affected cat and 30.6 in a normal age-matched control (NC). The L-iduronidase activity was slightly increased. Quantitation of total glycosaminoglycans (GAGs) revealed a 4.5-fold increase in the affected cat as compared with NC, while electrophoretic run of specific GAGs [chondroitin sulphate (CA); hyaluronan (HA); heparan sulphate (HS); dermatan sulphate (DS); keratan sulphate (KS)] performed on a cellulose acetate sheet, showed a striking increase in the DS band. On densitometric analysis of the electrophoretic run stained with Alcian Blue 8GX, the absorption of DS was eight-fold increased as compared with NC. The clinical and morphological features, and the biochemical findings, were consistent with the diagnosis of feline mucopolysaccharidosis VI.

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Mucopolysaccharidosis VII

Domestic


Fyfe JC, Kurzhals RL, Lassaline ME, Henthorn PS, Alur PR, Wang P, Wolfe JH, Giger U, Haskins ME, Patterson DF, Sun H, Jain S, Yuhki N. 1999 Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII.Genomics. 58(2):121-8.

fyfe@cvm.msu.edu

A family of domestic cats was found that exhibited clinical and biochemical abnormalities consistent with mucopolysaccharidosis VII, an autosomal recessive lysosomal storage disorder caused by beta-glucuronidase deficiency. beta-Glucuronidase activity was undetectable in affected cat fibroblasts and restored by retroviral gene transfer of rat beta-glucuronidase cDNA. beta-Glucuronidase mRNA was normal in affected cat testis by Northern blot analysis. Normal feline beta-glucuronidase cDNA was cloned and characterized, and amplified from affected cat fibroblasts by reverse transcription coupled polymerase chain reaction. There was a G-to-A transition in the affected cat cDNA that predicted an E351K substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression studies. Multiple species comparison and the crystal structure of human beta-glucuronidase indicated that E351 is a highly conserved residue most likely essential in maintenance of the enzyme's conformation. BssSI digestion of polymerase chain reaction products amplified from genomic DNA indicated that affected cats were homozygous and cats with half-normal beta-glucuronidase activity were heterozygous for the missense mutation. Carriers identified in this manner produced affected kittens in prospective breedings, and a feline MPS VII breeding colony has been established.

 

Muscular dystrophy

Maine Coon

Laminin alpha2 deficiency-associated muscular dystrophy

Poncelet L, Resibois A, Engvall E, Shelton GD. 2003 Laminin alpha2 deficiency-associated muscular dystrophy in a Maine coon cat. J Small Anim Pract. 44(12):550-2.

A European case of laminin alpha2 deficiency-associated muscular dystrophy in a 12-month-old, female Maine coon pedigree cat is reported. The history and eventual clinical presentation of this cat differed from those of two cats reported in the USA. In this case, the myopathy was characterised by progressively worsening weakness, muscle atrophy and joint contracture. Tendon reflexes were diminished, and motor nerve conduction velocities were slowed. Muscle biopsy demonstrated a dystrophic phenotype with endomysial fibrosis. Occasional thinly myelinated nerve fibres were present within a peripheral nerve specimen. Poorly myelinated fibres were also found at the root level on necropsy specimens. Immunohistochemical staining revealed the absence of laminin alpha2. The cat's family history did not indicate genetic transmission of the disease.

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Myocardial disease

Feline myocardial disease (cardiomyopathy) includes hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and dilated cardiomyopathy (DCM). It is the most common cardiac disorder observed in cats (Ferasin, 2009).

Ferasin (2009) provides best review of feline myocardial disease this webmaster has ever seen.

Clinical signs: heart murmur (60% cases), dyspnoea (50%), tachycardia (30%) lethargy (20%) hypotension (15%), poor body condition (10%), ascites (10%), arrythmia (10%), collapse (10%), abnormal respiratory sounds (10%), hindlimb paresis (7.5%), bradycardia (5.5%), muffled heart sounds (5.0%) Ferasin (2009).

Breeds: British Shorthair, Maine Coons, Norwegian Forest Cats, Ragdolls

Mode of inheritance (HCM) : autosomal dominant mode in Maine Coon and maybe also in British Shorthair and Ragdolls (Ferasin, 2009)

Reference

Ferasin L. 2009  Feline myocardial disease. 1: Classification, pathophysiology and clinical presentation.  J Feline Med Surg.  11(1):3-13.

 

Myopathy

Devon Rex, Maine Coon
 

N

Neutrophil granulation anomaly

Niemann-Pick disease - see sphingomyelinase deficiency

 

Neutrophil granulation anomaly

Birman

 

References

Hirsch VM, Cunningham TA. 1984 Hereditary anomaly of neutrophil granulation in Birman cats. Am J Vet Res. 45(10):2170-4.

A hereditary anomaly of neutrophil granulation in purebred Birman cats was described with respect to genetic, electron microscopic, histochemical, and functional characters. The trait was inherited in an autosomal recessive manner and was prevalent in the population studied. Affected cats had fine eosinophilic granules in the cytoplasm of neutrophils. The granules had normal morphology as determined by electron microscopy and did not stain for acid mucopolysaccharide. Bactericidal activity, phagocytosis, and oxidative function of affected neutrophils were not different from those of unaffected neutrophils. The anomaly was concluded to be an alteration in the content of lysosomal granules with increased affinity for acidic dyes.

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O

Ocular abnormalities and disease

Osteochondromatosis

Osteodystrophy
 

Ocular abnormalities and disease

Burmese, Himalayan, Persian, Siamese

 

References

Glaze MB. 2005 Congenital and hereditary ocular abnormalities in cats.Clin Tech Small Anim Pract. 20(2):74-82.

mglaze3937@aol.com

Congenital and inherited ocular diseases are reported less frequently in the cat than the dog. The 2 species also differ in their array of disorders, with familiar canine abnormalities like cataracts overshadowed by unique feline diseases such as eyelid agenesis and corneal sequestration. Organized according to the primary ocular structure affected and commingling congenital and inherited disorders in each section, the review begins with multiple ocular anomalies and their impact on globe-orbit relationship. Adnexal disorders include eyelid agenesis, entropion, dermoid, and nictitans gland protrusion. Corneal abnormalities range from the routine sequestrum and PPM-related opacity to those rare infiltrates accompanying inborn errors of metabolism. Brief descriptions of uveal anomalies, primary glaucoma, cataracts, and lens luxations follow. Retinal dysplasia and progressive retinal atrophy complete the summary. Suspicions of heritability are often based on small numbers of animals in sporadic reports of ocular disease, but the Persian, Burmese, and Siamese are among the breeds repeatedly linked with one or more of these disorders.


Narfstrom K. 1999 Hereditary and congenital ocular disease in the cat.J Feline Med Surg. 1 (3):135-41.

The aim of this review of hereditary and congenital ocular disease in cats is to present an overview of the most common disorders seen in this species, the pathogenesis of the problems and wherever possible, how they are treated. Several defects are common in breeds such as the Persian, Himalayan and Burmese cats and affect the anterior segment of the eye. Examples are agenesis of the eyelids, dermoids, entropion and corneal sequestrum. Other problems such as cataracts, lens luxation and retinal dysplasia, cause problems of the intraocular structures, but are less common in cats compared to dogs. Finally, various parts of the retina and in some diseases other parts of the eye, are specifically affected by hereditary diseases. Examples of these are lysosomal storage disease, Chediak-Higashi syndrome and progressive rod cone degeneration and rod cone dysplasia. Research of the latter two hereditary diseases, both described in the Abyssinian breed of cat, have made affected individuals important animal models for research into comparable diseases of humans.

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Osteochondromatosis


Levitin B, Aroch I, Aizenberg I, Foreman O, Shamir M. 2003 Linear osteochondromatosis in a cat.Vet Radiol Ultrasound. 2003 Nov-Dec;44(6):660-4.

A domestic shorthair cat was presented with quadriparesis and lumbar hyperesthesia that progressed over 4 months. There were linear and amorphous radiopaque masses throughout the soft tissue surrounding the long bones, vertebral bodies, ribs, pelvis, and scapula. The diagnosis of osteochondromatosis was confirmed by histopathology. Unlike previously reported patients with osteochondromatosis, most of the calcified masses in this cat were not connected to the periosteum; some were linear and were arranged parallel to the long bones involved.


Osteodystrophy

Scottish Fold

 

Reference


Mathews KG, Koblik PD, Knoeckel MJ, Pool RR, Fyfe JC.1995 Resolution of lameness associated with Scottish fold osteodystrophy following bilateral ostectomies and pantarsal arthrodeses: a case report.J Am Anim Hosp Assoc. 31(4):280-8.

Bilateral hind-limb lameness, associated with tarsal exostoses in a Scottish fold diagnosed as having Scottish fold osteodystrophy, resolved following staged bilateral ostectomies and pantarsal arthrodeses. Degenerative changes in the phalangeal joints of the hind limbs have progressed radiographically, but lameness has not recurred 48 weeks following the second arthrodesis. Additional skeletal abnormalities were detected radiographically in both carpi and in several caudal vertebrae. A partial, left-sided conduction deafness was diagnosed by evaluating brain stem auditory-evoked responses.

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P

Patent ductus arteriosis

Pelger-Huet anomaly

Polycystic kidney disease

Polyneuropathy

Porphyria

Progressive retinal atrophy (PRA)

Pyruvate kinase deficiency

 

Patent ductus arteriosis


Straw RC, Aronson EF, McCaw DL. 1985 Transposition of the great arteries in a cat. J Am Vet Med Assoc. 187(6):634-6.

Transposition of the great arteries, a congenital cardiac disorder, was diagnosed in a 4-month-old domestic short-haired kitten. Angiography revealed a patent ductus arteriosis, with the pulmonary artery originating from the left ventricle and the aorta originating from the right ventricle. Blood gas analysis suggested a high ventricular septal defect. Necropsy confirmed the diagnosis.

 

Pelger-Huet anomaly

DSH,

Autosomal dominant inherited disorder. Homozygous form is lethal. Heterozygote cats show granulocyte hypo-segmentation. Cells usually classified as immature or band neutrophils, but appear to have normal function.

 

Polycystic kidney disease

Persian, Exotic shorthair

Polycystic kidney disease (PKD) is an inherited condition of cats and humans.

 

In Persians, the condition has been shown to be inherited as a single autosomal dominant gene. It is estimated over 37% of Persians have PKD1, a breed that accounts for nearly 80% of the cat fancy.

Diagnosis is by ultrasound. A DNA test is available from the Veterinary Genetics Laboratory (VGL) at the University of California, Davis. All that is required is a swab of the buccal mucosa, instructions and a submission form can be found on the VGL website.

The Feline Advisory Bureau runs a PKD negative cat register. For screening by ultrasound, cats need to be at least 10 months old, whereas screening for the PKD1 gene can be done as soon as a DNA sample can be obtained. Gene test submission forms can be downloaded from the Feline Advisory Bureau website.

 

References

Greco DS. 2001 Congenital and inherited renal disease of small animals.Vet Clin North Am Small Anim Pract. 31(2):393-9, viii.

dgreco@vth.colostate.edu

Congenital renal diseases are present at birth and may be determined genetically; familial renal disorders occur in related animals with a higher frequency than would be expected by chance, and frequently are inherited. The most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's syndrome). This article alerts the veterinarian to commonly observed congenital and hereditary conditions of the kidneys in small animals.

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Polyneuropathy

see also sphingomyelinase deficiency

 


Porphyria

Siamese


Giddens WE Jr, Labbe RF, Swango LJ, Padgett GA. 1975 Feline congenital erythropoietic porphyria associated with severe anemia and renal disease. Clinical, morphologic, and biochemical studies.Am J Pathol. 80(3):367-86.

A feline erythropoietic porphyria was studied in an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia, hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries) and ischemic tubular injury. There was thickening of tubular basement membranes and tubular epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter in cytoplasmic and extracellular locations.

 

Progressive retinal atrophy (PRA) - see also retinal dystrophy

Abysinnian, Persian

Clinical signs: bilateral, leads to blindness. In Abysinnian, usually present by 3-4 years of age, earliest report only 7 months old. In Persians, pupillary light reflexes (PLR) were reduced as early as 16 weeks of age and diminution of the extent and speed of the PLR could be detected by the discerning as early as 2-3 weeks of age.

Mode of inheritance: autosomal recessive

 

References

Barnett KC, Curtis R. 1985 Autosomal dominant progressive retinal atrophy in Abyssinian cats.J Hered. 76(3):168-70.

Hereditary progressive retinal atrophy in Abyssinian cats in England is recorded. It is compared with another hereditary retinopathy in the same breed in Sweden and it is concluded that these are two distinct conditions, one occurring at an early age in kittens with an autosomal dominant mode of inheritance, the other occurring in young adult cats due to an autosomal recessive gene. The two diseases are bilateral, progressive, and of the generalized type, and are similar ophthalmoscopically.


Djajadiningrat-Laanen SC, Vaessen MM, Stades FC, Boeve MH, van de Sandt RR. 2002 Progressive retinal atrophy in Abyssinian and Somali cats in the Netherlands (1981-2001) Tijdschr Diergeneeskd. 127(17):508-14.

From 1981 to 2001, 248 Abyssinian and 127 Somali cats in the Netherlands were examined for hereditary eye disease. Distinct ophthalmoscopic signs consistent with hereditary progressive retinal atrophy (PRA) were observed in 11 Abyssinian cats, and subtle signs in 3 Abyssinian cats. A familial relationship was detected in 13 out of 14 of these cats, which supports a hereditary basis to the condition. Distinct funduscopic signs of retinal degeneration were observed at a median age of 4 years. One cat with advanced retinal degeneration was only 7 months old, whereas the remaining 10 cats were between 2 and 12 years old at the time of diagnosis. These differences in the age of onset are suggestive of at least two types of PRA occurring in Abyssinian cats in the Netherlands: a dysplastic, early-onset and a late-onset retinal degeneration. A large-scale and systematic examination programme for hereditary eye disease will be necessary to assess the incidence of PRA in the Dutch population of Abyssinian and Somali cats as a whole, and to provide a basis for a preventive breeding programme.


Narfstrom K. 1983 Hereditary progressive retinal atrophy in the Abyssinian cat. J Hered. 74(4):273-6.

Progressive retinal atrophy (PRA), a hereditary eye disease leading to blindness, was found in the Abyssinian breed of cat. Sixty-eight cases of a bilateral generalized retinopathy, at different stages of the disease process, were seen in the breed during ophthalmoscopic examinations of cats throughout Sweden during a 2-year period. Forty-five percent of cats aged 2 years or older were affected in the examined group. The earliest case was diagnosed in a 16-month-old cat. At the age of 3-4 years a bilateral retinal atrophy was usually present in affected cats. Genetic analysis indicates that PRA in the Abyssinian cat is caused by an autosomal recessive gene.

 


Narfstrom K. 1985 Progressive retinal atrophy in the Abyssinian cat. Clinical characteristics.Invest Ophthalmol Vis Sci. 26(2):193-200.

Ninety-four cases of a hereditary retinal degeneration in household Abyssinian cats were found in Sweden, mainly during a 3-year period. The disease was investigated by ophthalmoscopy, fluorescein angiography, electroretinography, and light microscopy. A bilateral retinopathy was usually first seen in affected cats at the age of 1.5-2 years. Fluorescein angiography did not demonstrate abnormalities of etiological significance to the disease process. A reduction mainly of a- and b-wave amplitudes in the ERG indicated a generalized photoreceptor disease. Light microscopy showed that the photoreceptor layer was primarily affected, while other retinal layers were mainly normal. The midperipheral and peripheral retina was affected more severely than the retina of the posterior pole until late stages of disease, when there was a generalized loss of photoreceptors. The clinical and laboratory findings suggest that PRA in these Abyssinian cats is a heritable photoreceptor degenerative disease with a fairly slow rate of progression.

 

Rah H, Maggs DJ, Blankenship TN, Narfstrom K, Lyons LA. 2005 Early-onset, autosomal recessive, progressive retinal atrophy in Persian cats. Invest Ophthalmol Vis Sci. 46(5):1742-7

PURPOSE: An early-onset retinal degenerative disease has been identified in Persian cats. This study genetically, clinically, and histologically characterized the disease. A breeding colony was established to assist with identification of the causative gene and to provide a resource for vision research. METHODS: Cats were produced from testcross breedings. Kittens underwent serial ophthalmic and neuro-ophthalmic examinations. Globes were harvested from age-matched affected, obligate carrier, and control cats and were evaluated by light microscopy. Fluorescein angiography assessed retinal and choroidal vasculature. RESULTS: Test breedings confirmed an autosomal recessive mode of inheritance. Rate and extent of disease progression were similar among individual affected cats. The earliest clinical signs (reduced pupillary light reflexes) were seen at 2 to 3 weeks of age. Retinal degeneration was virtually complete by 16 weeks of age. Histologic changes progressed rapidly and paralleled clinical findings. Histologic lesions were limited to the photoreceptors, outer plexiform layer, and retinal pigment epithelium in all but the terminal stages, when subtle changes were noted within the inner nuclear layer. CONCLUSIONS: Characterized in this study was an autosomal recessive, early-onset, retinal degenerative disease in Persian cats that is likely to be more prevalent in this breed than previously suspected. This feline disease model may identify a new gene or provide biological insight into some forms of early-onset retinitis pigmentosa (RP) in humans and genetic retinal degenerations in other species. A breeding colony that will assist in the identification of the causative gene has been established and is available for studies in vision research.

 

Sarva R.1986 Progressive retinal atrophy in the Abyssinian cat. Nord Vet Med. 38(6):388-93.

Eight cases of hereditary progressive retinal atrophy in Abyssinian cats in Denmark are reported. Pedigree studies indicate direct lineage to affected cats of the same breed in Sweden. The disease is bilateral, progressive, and of the generalized type, and ultimately leads to blindness.

 

Pyruvate kinase deficiency

Abyssinian, DSH, Somali

Clinical signs: intermittent haemolytic anaemia, jaundice, splenomegaly

Mode of inheritance: autosomal recessive

Link to testing laboratory: Josephine Deubler Genetic Testing Laboratory, Pennsylvania, USA.

Link to submission form for genetic test from the Josephine Deubler Genetic Testing Laboratory, Pennsylvania, USA.

 

References

Mansfield CS, Clark P. 2005 Pyruvate kinase deficiency in a Somali cat in Australia. Aust Vet J. 83(8):483-5.

R

Renal calculi

Retinal atrophy - see Progressive retinal atrophy (PRA)

Retinal degeneration - see Mucolipidosis II

Retinal dystrophy

Rod cone degeneration/rod cone dysplasia

 

Renal calculi

Crossbred cats were significantly less likely to have renal calculi than were other breeds.

Birman, Tonkinese


Ling GV, Ruby AL, Johnson DL, Thurmond M, Franti CE. 1998 Renal calculi in dogs and cats: prevalence, mineral type, breed, age, and gender interrelationships (1981-1993).J Vet Intern Med. 1998 Jan-Feb;12(1):11-21.

gvling@ucdavis.edu

Three hundred seventeen specimens of urinary calculi of renal origin from 214 female dogs and 103 male dogs, and 71 specimens of urinary calculi of renal origin from 38 female cats and 33 male cats were submitted for mineral analysis between July 1, 1981, and December 31, 1993. Among dogs, 45 breeds were affected with renal calculi. Thirty-three breeds and a crossbred group were represented among females, but 8 breeds and the crossbred group accounted for 81% of the total. Among male dogs, 30 breeds and a crossbred group were represented, but 7 breeds and the crossbred group accounted for 69% of the total. Among cats, 10 breeds and a crossbred group were represented. Dogs and cats with renal calculi were older than those of 2 comparison population groups. More than one-half of the renal calculi in both dogs and cats were from the 1st known episode of urolithiasis. The risk of formation of renal calculi was found to be higher for cats than for dogs, when compared to other stone-forming cats and dogs (approximately 4.95 per 100 stone-forming cats and 2.88 per 100 stone-forming dogs). Among dogs, breeds at highest risk of developing renal calculi were Miniature Schnauzers, Shih Tzus, Lhasa Aposos, Yorkshire Terriers, and female Pugs. Also at high risk were male Dalmatians and male Basset Hounds. Among small dogs, females generally were at higher risk of developing renal calculi than were males. Regardless of size, terrier breed males generally were at higher risk of developing renal calculi. Breeds of dogs at low risk for development of renal calculi included crossbreds. German Shepherd Dogs, Labrador Retrievers, Golden Retrievers, and female Dachshunds. When only 1 kidney was involved, the risk of left renal calculus was greatest for both dogs and cats, but bilateral renal involvement was relatively common in both species (19% and 9%, respectively). Among dogs, specimens composed of 1 mineral substance (e.g., struvite) occurred more often in males (58.3%) than in females (37.9%). Female dogs formed renal calculi containing struvite or oxalate more often than did males; males formed calculi containing urate more often than did females. Calculi containing oxalate, apatite, or some combination of these minerals predominated among cats; only 1 specimen from 38 female cats and only 4 specimens from 33 male cats contained neither oxalate nor apatite. Crossbred cats were significantly less likely to have renal calculi than were other breeds. A single renal calculus specimen was identified in several uncommon breeds including Tonkinese and Birman cats, and Affenpinscher, Clumber Spaniel, English Shepherd, and Field Spaniel dogs. No significant differences were observed between male and female dogs or between male and female cats with regard to mineral type of the specimen and the presence of urinary tract infection.

 

Retinal dystrophy

Abysinnian

Clinical signs: marked dilatation of the pupils, impairment of the pupillary light reflex, and nystagmus

Mode of inheritance: autosomal dominant

 

Curtis R, Barnett KC, Leon A. 1987 An early-onset retinal dystrophy with dominant inheritance in the Abyssinian cat. Clinical and pathological findings.Invest Ophthalmol Vis Sci. 28(1):131-9.

The clinical and pathological features of an early-onset autosomal dominant photoreceptor degeneration in the Abyssinian cat are described. Ophthalmoscopic evidence of retinal disease at 8-12 weeks of age was always preceded by marked dilatation of the pupils, impairment of the pupillary light reflex, and nystagmus. The electroretinogram was unrecordable in all but one of the affected individuals examined. Abnormal photoreceptor development was observed by both light and electron microscopy in retinas of a 22-day-old kitten; in this individual, no outer segment material was detected, and inner segments showed impaired development which was more severe towards the posterior pole. In a 40-day-old kitten, the inner segments were relatively well-formed, whereas the outer segments, though present, showed marked disorganization and degenerative change. The retinas of older individuals showed more advanced photoreceptor degeneration, with thinning of the neural retina. This early-onset retinopathy, which may be classified as a rod-cone dysplasia, is distinct from the hereditary retinal dystrophy (progressive retinal atrophy) previously described in this breed. The gene symbol Rdy has been adopted.



Gould DJ, Sargan DR. 2002 Autosomal dominant retinal dystrophy (Rdy) in Abyssinian cats: exclusion of PDE6G and ROM1 and likely exclusion of Rhodopsin as candidate genes.Anim Genet. 33(6):436-40.

d.j.gould@bris.ac.uk

Retinal dystrophy (Rdy) is an autosomal dominant photoreceptor dysplasia of Abyssinian cats and a model for autosomal dominant retinitis pigmentosa (ADRP) in man. We have pursued a candidate gene approach in the search for the causal mutation in Rdy. The genes RHO (encoding rhodopsin), ROM1 (encoding the structural retinal outer-membrane protein-1) and PDE6G (encoding the gamma subunit of the visual transduction protein cyclic guanosine monophosphate-phosphodiesterase) were polymerase chain reaction-amplified from normal feline genomic DNA. Leader, coding and 3' untranslated regions of each gene, and parts of introns were sequenced. Single-stranded conformation polymorphism (SSCP) analysis of Rdy-affected and normal cats was used to identify intragenic polymorphisms within ROM1 and PDE6G. DNA sequencing of all three genes in Rdy-affected cats was used to confirm results from SSCP. For both ROM1 and PDE6G polymorphisms identified by SSCP and sequencing showed disconcordance between the polymorphism and the disease phenotype within an Rdy disease pedigree. SSCP analysis of RHO performed across the 5' untranslated region, the entire coding sequence and the intron/exon boundaries in Rdy-affected and control cats failed to identify any intragenic polymorphisms that could be used for linkage analysis. DNA sequencing of these regions showed no differences between Rdy-affected and control cats. Mutations in ROM1 or in PDE6G are not causative of feline Rdy. The absence of potentially pathogenic polymorphisms in sequenced portions of the RHO gene makes it unlikely that a mutation in this gene is the cause of Rdy.

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Progressive rod cone degeneration and rod cone dysplasia

Abysinnian

Clinical signs: the retina is, in most cases, ophthalmoscopically normal until the age of 1.5-2 years. The retinal changes that then appear are slowly progressive and lead to a generalized retinal atrophy in another 2-4 years.

 

Reference


Narfstrom K, Nilsson SE. 1987 Hereditary rod-cone degeneration in a strain of Abyssinian cats. Prog Clin Biol Res. 247:349-68.

The retinal disease found in this strain of Abyssinian cats is a heritable disorder, primarily affecting the photoreceptors. The retina is, in most cases, ophthalmoscopically normal until the age of 1.5-2 years. The retinal changes that then appear are slowly progressive and lead to a generalized retinal atrophy in another 2-4 years. It is obvious that this cat retinal degeneration shows many similarities to human Retinitis Pigmentosa. Just as in RP the midperiphery/periphery is most severely affected at the earlier stages, and with progression of disease alterations become generalized, the central retina being the best preserved area until the very late stage. Rods are affected prior to cones, but later in the disease there is an involvement of both rods and cones. Also, the disease process is slow, starting off from an ophthalmoscopically normal appearing retina. This strain of Abyssinian cats, affected by the presently described retinal disease, therefore has the potential of becoming a new animal model in the study of hereditary visual cell disease processes.

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S

Sacrocaudal dysgenesis

Sandhoff disease - see GM2 gangliosidosis

Sphingomyelinase deficiency

Staphyloma

 

Sacrocaudal dysgenesis

Manx

 

Clinical signs:

Mode of inheritance: autosomal dominant

Jones BR 2004 The nervous system. Feline Medicine and Therapeutics. Third Edition Eds (Chandler EA. Gaskell CJ & Gaskell, RM) 125-171

 

Sphingomyelinase deficiency (Niemann-Pick disease)

 

Clinical signs: hepatosplenomegaly, progressive neuromuscular disease

Mode of inheritance: autosomal recessive

 

References

Brown DE, Thrall MA, Walkley SU, Wurzelmann S, Wenger DA, Allison RW, Just CA. 1996 Metabolic abnormalities in feline Niemann-Pick type C heterozygotes. Inherit Metab Dis. 19(3):319-30.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis results from defective intracellular transport of unesterified cholesterol. The primary molecular defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired, resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular inclusions immunoreactive for GM2-ganglioside. Ultrastructural studies provided evidence of storage in liver and brain. We believe these morphological and biochemical findings are the first example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage disease.

Cuddon PA, Higgins RJ, Duncan ID, Miller SP, Parent JM, Moser AB. Polyneuropathy in feline Niemann-Pick disease.Brain. 1989 112 ( Pt 6):1429-43.

Two related cats, aged 5 months and 7 months, and 1 unrelated cat, aged 4 months, presented with signs of a progressive neuromuscular disease. Detailed electrophysiological studies suggested a primary demyelinating polyneuropathy, which was confirmed by muscle and nerve biopsies and on necropsy examination. Light and electron microscopic findings indicated a lysosomal storage disease, which was diagnosed as sphingomyelinase deficiency (Niemann-Pick disease) by enzyme analysis and lipid fractionation, although significant biochemical differences existed between the 2 related cats and the third cat. Several lines of evidence suggest that these 2 related cats were affected with a variant of type A Niemann-Pick disease, whereas cat 3 represented classic Niemann-Pick disease type A.

 

Garver WS, Somers K, Krishnan K, Mitchell T, Heidenreich RA, Thrall MA. 2002 The Niemann-Pick C1 protein in feline fibroblasts.Mol Genet Metab. 76(1):31-6.

wgarver@peds.arizona.edu

Niemann-Pick type C (NPC) disease is a rare inherited metabolic disorder characterized by hepatosplenomegaly, progressive neurodegeneration, and storage of lipids such as cholesterol and glycosphingolipids in most tissues. The current study was conducted to characterize the Niemann-Pick C1 (NPC1) protein in feline fibroblasts. This was accomplished by generating rabbit polyclonal antibodies against a peptide corresponding to amino acids 1256-1275 of the feline NPC1 protein. The results obtained using immunoblot analysis identified two major proteins that migrated at approximately 140 and 180 kDa. These two proteins were absent when immunoblots were incubated in the presence of feline NPC1 antibody and immunizing peptide, or preimmune serum. Fluorescence microscopy of feline fibroblasts incubated with the feline NPC1 antibody revealed granular staining within the perinuclear region of the cell. This granular staining was diminished when feline fibroblasts were incubated in the presence of feline NPC1 antibody and immunizing peptide, or was completely absent when feline fibroblasts were incubated in the presence of preimmune serum. Additional studies using double-labeled fluorescence microscopy indicated that feline NPC1 partially colocalized with markers for late endosomes/lysosomes, endoplasmic reticulum, and microtubules, but not the trans-Golgi network. In summary, the results presented in this report demonstrate that the NPC1 protein in feline fibroblasts has a similar distribution as that previously described for human and murine fibroblasts.


Somers KL, Brown DE, Fulton R, Schultheiss PC, Hamar D, Smith MO, Allison R, Connally HE, Just C, Mitchell TW, Wenger DA, Thrall MA. 2001 Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.J Inherit Metab Dis. 24(4):427-36.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.

Somers KL, Royals MA, Carstea ED, Rafi MA, Wenger DA, Thrall MA. 2003 Mutation analysis of feline Niemann-Pick C1 disease.Mol Genet Metab. 79(2):99-103.

klsomers@colostate.edu

Niemann-Pick C (NPC) disease is an autosomal recessive neurovisceral lysosomal storage disorder that results in defective intracellular transport of cholesterol. The major form of human NPC (NPC1) has been mapped to chromosome 18, the NPC1 gene (NPC1) has been sequenced and several mutations have been identified in NPC1 patients. A feline model of NPC has been characterized and is phenotypically, morphologically, and biochemically similar to human NPC1. Complementation studies using cultured fibroblasts from NPC affected cats and NPC1 affected humans support that the gene responsible for the NPC phenotype in this colony of cats is orthologous to human NPC1. Using human-based PCR primers, initial fragments of the feline NPC cDNA were amplified and sequenced. From these sequences, feline-specific PCR primers were generated and designed to amplify six overlapping bands that span the entire feline NPC1 open reading frame. A single base substitution (2864G-C) was identified in NPC1 affected cats. Obligate carriers are heterozygous at the same allele and a PCR-based assay was developed to identify the geneotype of all cats in the colony. The mutation results in an amino acid change from cysteine to serine (C955S). Several of the mutations identified in people occur in the same region. Marked similarity exists between the human and feline NPC1 cDNA sequences, and is greater than that between the human and murine NPC1 sequences. The human cDNA sequence predicts a 1278aa protein with a lysosomal targeting sequence, several trans-membrane domains and extensive homology with other known mediators of cholesterol homeostasis.

 

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Staphyloma

 

Reference


Skorobohach BJ, Hendrix DV .Staphyloma in a cat .Vet Ophthalmol. 2003 Jun;6(2):93-7.

bskorobo@utk.edu

A unilateral scleral staphyloma in an 18-month-old, female spayed Domestic Short-haired cat was treated with excision, primary closure and fascial graft. Other ocular abnormalities noted on examination included iris coloboma, anterior cortical cataract, focal lens equator flattening and retinal dysplasia. The staphyloma was presumed to be congenital in origin.

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T


Thromboembolism
Type IV glycogen storage disease 

 

Thromboembolism

Abyssinian, Birman, Ragdoll


Smith SA, Tobias AH, Jacob KA, Fine DM, Grumbles PL. 2003 Arterial thromboembolism in cats: acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases.J Vet Intern Med. 17(1):73-83.

Records of 127 cats with arterial thromboembolism (ATE) were reviewed. Abyssinian, Birman, Ragdoll, and male cats were overrepresented. Tachypnea (91%), hypothermia (66%), and absent limb motor function (66%) were common. Of 90 cats with diagnostics performed, underlying diseases were hyperthyroidism (12), cardiomyopathy (dilated [8], unclassified [33], hypertrophic obstructive [5], hypertrophic [19]), neoplasia (6), other (4), and none (3). Common abnormalities were left atrial enlargement (93%), congestive heart failure (CHF, 44%), and arrhythmias (44%). Of cats without CHF, 89% were tachypneic. Common biochemical abnormalities were hyperglycemia, azotemia, and abnormally high serum concentrations of muscle enzymes. Of 87 cats treated for acute limb ATE, 39 (45%) survived to be discharged. Significant differences were found between survivors and nonsurvivors for temperature (P < .00001), heart rate (P = .038), serum phosphorus concentration (P = .024), motor function (P = .008), and number of limbs affected (P = .001). No significant difference was found between survivors and nonsurvivors when compared by age, respiratory rate, other biochemical analytes, or concurrent CHE A logistic regression model based on rectal temperature predicted a 50% probability of survival at 98.9 degrees F (37.2 degrees C). Median survival time (MST) for discharged cats was 117 days. Eleven cats had ATE recurrences, and 5 cats developed limb problems. Cats with CHF (MST: 77 days) had significantly shorter survival than cats without CHF (MST: 223 days; P = .016). No significant difference was found in survival or recurrence rate between cats receiving high-dose aspirin (> or = 40 mg/cat q72h) and cats receiving low-dose aspirin (5 mg/cat q72h). Adverse effects were less frequent and milder for the lower dosage.

Type IV glycogen storage disease - see glycogen storage diseases

U

Urinary tract - lower


Kruger JM, Osborne CA, Lulich JP, Oakley RE. 1996 Inherited and congenital diseases of the feline lower urinary tract.Vet Clin North Am Small Anim Pract. 26(2):265-79.

Congenital urinary tract disorders of young cats may result from heritable (genetic) or acquired disease processes that affect differentiation and growth of the developing urinary tract, or from similar disease processes that eventually affect the structure or function of the mature urinary system. Although congenital diseases of the feline lower urinary tract are uncommon, clinical signs associated with these anomalies may be indistinguishable from those of other acquired causes of lower urinary tract disease. Early detection and proper management of congenital disorders may result in restoration of urinary bladder and urethral function and/or progressive urinary tract dysfunction.


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V

Ventricular septal defect

Vitamin K-dependent multifactor coagulopathy - see coagulopathies

 

Ventricular septal defect - also see Patent ductus arteriosis

Domestic

Thomas WP. 2005 Echocardiographic diagnosis of congenital membranous ventricular septal aneurysm in the dog and cat. J Am Anim Hosp Assoc. 41 (4): 215-20.

Membranous ventricular septal aneurysm was diagnosed by echocardiography in 17 dogs and three cats. The aneurysm appeared as a thin membrane protruding into the right ventricle from the margins of a congenital ventricular septal defect (VSD). The aneurysm was intact in nine dogs and two cats and perforated by a small VSD in eight dogs and one cat. Other congenital heart defects were present in seven dogs. In all animals, the aneurysm was an incidental finding observed during echocardiographic examination, and it did not appear to directly cause any cardiac dysfunction.

X

Xanthomata - see Lipoprotein lipase deficiency

 

4 Nov 2011

 

 

 

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