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:
Anaemia - see pyruvate kinase deficiency
Ataxia - see Mucolipidosis II
Axonopathy- see distal axonopathy
Chew DJ, DiBartola SP, Boyce JT, et al. 1982. Renal amyloidosis in related Abyssinian cats. JAVMA 181 139
Clinical signs: progressively worsening neurological signs including tremors, loss of balance, and nystagmus from 4 to 18 weeks of age.
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.
Cataracts - see Chediak-Higashi syndrome
Christmas disease - see Haemophilia B
Corneal clouding - see Mucopolysaccharidosis I.
Cutaneous asthenia - see Ehlers-Danlos syndrome.
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.
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.
Smoke blue Persians
Clinical signs: cataracts, nystagmus
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
Vitamin K-dependent multifactor
Clinical signs: haemorrhage, prolonged clotting times, response to Vitamin K.
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.
Jones BR, Gruffydd-Jones TJ, Sparkes AH. 1991 Congenital hypothyroidism in the cat. FAB Bulletin 28 1 12
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
Davies White Veterinary Specialists, Manor Farm Business Park, Higham Gobion SG3 5HR, UK. email@example.com
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.
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
Dermatosparaxis - see Ehlers-Danlos syndrome
See article on heredity of this by Roy Robinson.
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.
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.
Most diaphragmatic hernias are traumatic in origin (usually post road accident).
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
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.
Kittens of 8 to 10 weeks of age with slowly progressive posterior ataxia.
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.
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.
Devon Rex, Persian and Siamese-type
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.
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.
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.
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.
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.
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.
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.
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
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
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.
Gingivitis - hyperplastic, early onset
Clinical signs: vomiting, hematemesis, intermittent melena, and weight loss
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.
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.
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.
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
In G(M2) gangliosidosis variant
0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase
(EC 184.108.40.206) 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).
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
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.
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.
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.
Williams CA, Aller MS. 1992 Gingivitis/stomatitis in cats. Veterinary Clinics of North America. 22 6 1361 - 1383
Type IV glycogen storage disease
Norwegian Forest Cats
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.
Hemophilia A (factor VIII deficiency)
Heart defect - see Ventricular Septal Defect
British shorthair, Domestic
Clinical signs: regenerative anaemia, haemorrhage, subcutaneous haematomas, prolonged bleeding times, shifting lameness.
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.
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
Mode of inheritance: autosomal recessive
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.
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.
Clinical signs: hindlimb lameness, history of constipation
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.
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)
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.
Clinical signs: periodic muscle weakness and cervical ventroflexion, onset can be as early as 10 weeks old.
Mode of inheritance: homozygote recessive
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.
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.
Laminin alpha2 deficiency - see muscular dystrophy
Clinical signs: fasting hyperlipaemia, lipaemia retinalis, peripheral neuropathies and subcutaneous xanthomas
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.
(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.
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.
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.
Vacuolation of lymphocytes and monocytes.
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.
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
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 220.127.116.11) 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.
The mucopolysaccharidoses (MPS) are inherited metabolic disorders resulting from the defective catabolism of glycosaminoglycans.
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.
Clinical signs: corneal clouding
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.
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.
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.
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.
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.
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.
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.
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)
Ferasin L. 2009 Feline myocardial disease. 1: Classification, pathophysiology and clinical presentation. J Feline Med Surg. 11(1):3-13.
Devon Rex, Maine Coon
Niemann-Pick disease - see sphingomyelinase deficiency
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.
Burmese, Himalayan, Persian, Siamese
Glaze MB. 2005 Congenital and hereditary ocular abnormalities in cats.Clin Tech Small Anim Pract. 20(2):74-82.
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.
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.
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.
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
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.
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.
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.
Greco DS. 2001 Congenital and inherited renal disease of small animals.Vet Clin North Am Small Anim Pract. 31(2):393-9, viii.
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.
see also sphingomyelinase deficiency
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.
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
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.
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.
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.
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.
Mansfield CS, Clark P. 2005 Pyruvate kinase deficiency in a Somali cat in Australia. Aust Vet J. 83(8):483-5.
Retinal atrophy - see Progressive retinal atrophy (PRA)
Retinal degeneration - see Mucolipidosis II
Crossbred cats were significantly less likely to have renal calculi than were other breeds.
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
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.
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.
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.
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.
Sandhoff disease - see GM2 gangliosidosis
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
Clinical signs: hepatosplenomegaly, progressive neuromuscular disease
Mode of inheritance: autosomal recessive
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
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.
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.
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.
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.
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.
Abyssinian, Birman, Ragdoll
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 , unclassified , hypertrophic
obstructive , hypertrophic ), 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.
Urinary tract - lower
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.
Vitamin K-dependent multifactor coagulopathy - see coagulopathies
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.
Xanthomata - see Lipoprotein lipase deficiency
4 Nov 2011
2000-2011 Dr. Diane Addie