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.
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Anaemia - see pyruvate kinase deficiency
Ataxia - see Mucolipidosis II
Axonopathy- see distal axonopathy
Abysinnian
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.
References
Vite
CH, McGowan JC, Braund KG, Drobatz KJ, Glickson JD, Wolfe JH, Haskins
ME. 2001 Histopathology, electrodiagnostic testing, and magnetic
resonance imaging show significant peripheral and central nervous
system myelin abnormalities in the cat model of alpha-mannosidosis.
J Neuropathol Exp Neurol. 60(8):817-28.
Alpha-mannosidosis is a disease caused by the deficient activity of alpha-mannosidase, a lysosomal hydrolase involved in the degradation of glycoproteins. The disease is characterized by the accumulation of mannose-rich oligosaccharides within lysosomes. The purpose of this study was to characterize the peripheral nervous system (PNS) and central nervous system (CNS) myelin abnormalities in cats from a breeding colony with a uniform mutation in the gene encoding alpha-mannosidase. Three affected cats and 3 normal cats from 2 litters were examined weekly from 4 to 18 wk of age. Progressively worsening neurological signs developed in affected cats that included tremors, loss of balance, and nystagmus. In the PNS, affected cats showed slow motor nerve conduction velocity and increased F-wave latency. Single nerve fiber teasing revealed significant demyelination/remyelination in affected cats. Mean G-ratios of nerves showed a significant increase in affected cats compared to normal cats. Magnetic resonance imaging of the CNS revealed diffuse white matter signal abnormalities throughout the brain of affected cats. Quantitative magnetization transfer imaging showed a 8%-16% decrease in the magnetization transfer ratio in brain white matter of affected cats compared to normal cats, consistent with myelin abnormalities. Histology confirmed myelin loss throughout the cerebrum and cerebellum. Thus, histology, electrodiagnostic testing, and magnetic resonance imaging identified significant myelination abnormalities in both the PNS and CNS that have not been described previously in alpha-mannosidosis.
Birman
Reference
Gunn-Moore
DA, Dodkin SJ, Sparkes AH. 2002 An unexpectedly high prevalence
of azotaemia in Birman cats. J Feline Med Surg. 4(3):165-6.
Blindness - see Mucolipidosis II and Progressive retinal atrophy
Cardiac defect - see Mucolipidosis II, and Patent Ductus Arteriosis and Ventricular Septal Defect
Cardiomyopathy - Hypertrophic cardiomyopathy
Cataracts - see Chediak-Higashi syndrome
Cerebellar degeneration - hereditary
Christmas disease - see Haemophilia B
Corneal clouding - see Mucopolysaccharidosis I.
Cutaneous asthenia - see Ehlers-Danlos syndrome.
Cerebellar degeneration - hereditary
Clinical signs: cerebellar dysfunction from the age of 7 to 8 weeks onward. Becomes progressively worse, but not fatal, between 1 and 2.5 months.
Mode of inheritance: autosomal recessive.
Inada S, Mochizuki M,
Izumo S, Kuriyama M, Sakamoto H, Kawasaki Y, Osame M. 1996 Study
of hereditary cerebellar degeneration in cats. Am J Vet Res. 57(3):296-301.
OBJECTIVE--To elucidate the
nature of ataxia observed in 3 cats spanning 2 generations. DESIGN--Experimental
breeding was attempted to confirm heritability of the disease and
establish the mode of inheritance; the original 3 cats and their
offspring were studied. ANIMALS--Seven diseased cats spanning 3
generations and 11 neurologically normal cats. PROCEDURE--Cats were
examined by use of the following methods: clinical observation,
hematologic and serum biochemical examinations, neurologic examination,
electrodiagnostics, magnetic resonance imaging, lysosomal enzyme
activity assay, horizontal transmission test, and virologic and
pathologic examinations. RESULTS--All kittens (1 male and 3 females)
obtained by backcrosses developed pure cerebellar dysfunction from
the age of 7 to 8 weeks onward. It became progressively worse, but
not fatal, between 1 and 2.5 months. Prenatal or perinatal infection
with feline panleukopenia virus, inherited lysosomal storage diseases,
including gangliosidosis and mannosidosis, and feline hereditary
neuroaxonal dystrophy were excluded. Magnetic resonance imaging
indicated that size of the cerebellum of diseased cats was markedly
reduced. Cerebellar cortical degeneration, especially with extensive
destruction of Purkinje cells, was observed microscopically. CONCLUSION--The
disease was concluded to be cerebellar degeneration of a new clinical
form in cats having an autosomal recessive mode of inheritance.
CLINICAL RELEVANCE--When cerebellar dysfunction is diagnosed in
a cat, hereditary cerebellar degeneration of this type should be
considered in the differential diagnosis.
Smoke blue Persians
Clinical signs: cataracts, nystagmus
References:
Collier LL, Bryan GM, Prieur DJ. 1979. Ocular manifestations of the Chediak-Higashi syndrome in four species of animals. JAVMA 175 587-590
Ocular examinations were performed on cattle, cats, mink, and mice affected with Chediak-Higashi syndrome (CHS). Bovine eyes were examined grossly and with an indirect ophthalmoscope, and Schirmer tear tests were performed. Feline eyes were examined grossly as well as with an indirect opthalmoscope and a slit lamp biomicroscope, and Schirmer tear tests were done on them. Postrotatory nystagmus was induced and measured in clinically normal Siamese cats, in clinically normal Persian and domestic short-haired cats, and in cats with CHS. Mink and mouse eyes were examined grossly with focal illumination. The animals with CHS had photophobia, pale irises, and fundic hypopigmentation associated with red fundic light reflections. Cats with CHS also had cataracts. Spontaneous nystagmus was observed in four of nine cats with CHS, and the duration of induced nystagmus was longer in the cats with CHS and in Siamese cats than in clinically normal cats that were not Siamese. Tear secretion appeared to be normal in all species of animals with CHS. The ocular manifestations of CHS in these animals were compared with those reported in man and were found to be similar.
Collier LC, King EJ, Prieur DJ. 1985 Tapetal degeneration in cats with Chediak-Higashi syndrome. Curr. Eye Res. 4 767-733
Kramer JW, Davis WC, Prieru DJ. 1977 The Chediak-Higashi syndrome of cats. Lab. Invest. 36 554-562
Coagulopathies - see also Hageman (coagulation factor XII) deficiency
Devon Rex
Vitamin K-dependent multifactor
coagulopathy
Devon Rex
Clinical signs: haemorrhage, prolonged clotting times, response to Vitamin K.
References:
Evans RJ. 1985 The blood and haemopoietic system. In Feline Medicine and Therapeutics. (Ed.) Chandler EA, Hilbery ADR, Gaskell CJ. 129-130
Littlewood JD, Shaw SC, Coombes LM.Vitamin K-dependent coagulopathy in a British Devon rex cat.J Small Anim Pract. 1995 Mar;36(3):115-8.Animal Health Trust, Newmarket, Suffolk.
Deficiencies of the vitamin
K-dependent coagulation factors were identified in a Devon rex cat
which had bled after castration. Haemorrhage was controlled by plasma
transfusion. Clotting times were normalised by oral administration
of vitamin K. This report confirms the existence of this bleeding
disorder in a Devon rex cat in the United Kingdom.
Maddison JE, Watson AD, Eade IG, Exner T.1990 Vitamin K-dependent multifactor coagulopathy in Devon Rex cats. J Am Vet Med Assoc. 197(11):1495-7. Department of Veterinary Clinical Sciences, University of Sydney, N.S.W., Australia.
A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder.
Soute BA, Ulrich MM, Watson AD, Maddison JE, Ebberink RH, Vermeer C. 1992 Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats.Thromb Haemost. 68(5):521-5. Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
Two Devon Rex cats from the
same litter, which had no evidence of liver disease, malabsorption
of vitamin K or chronic ingestion of coumarin derivatives, were
found to have plasma deficiencies of factors II, VII, IX and X.
Oral treatment with vitamin K1 resulted in the normalization of
these coagulation factors. After taking liver biopsies it was demonstrated
that the coagulation abnormality was accompanied by a defective
gamma-glutamyl-carboxylase, which had a decreased affinity for both
vitamin K hydroquinone and propeptide. This observation prompted
us to study in a well-defined in vitro system the possible allosteric
interaction between the propeptide binding site and the vitamin
K hydroquinone binding site on carboxylase. It was shown that by
the binding of a propeptide-containing substrate to gamma-glutamylcarboxylase
the apparent KM for vitamin K hydroquinone is decreased about 20-fold.
On the basis of these in vitro data the observed defect in the Devon
Rex cats can be fully explained.
Abysinnian
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
Persian
Featherstone
HJ, Sansom J.2004 Feline corneal sequestra: a review of 64 cases
(80 eyes) from 1993 to 2000.Vet Ophthalmol. 2004 Jul-Aug;7(4):213-27.
Davies White Veterinary Specialists, Manor Farm Business Park, Higham Gobion SG3 5HR, UK. hjf@vetspecialists.co.uk
Feline corneal sequestrum
is a common condition of the feline cornea. The purpose of this
study was to provide a detailed description of the clinical features
of the condition including the response to different management
options and to assess the rate of recurrence. The medical records
of 64 cases (80 eyes) of feline corneal sequestra that presented
to the Animal Health Trust from 1993 to 2000 were reviewed. Fifty-two
cases were reviewed retrospectively; 12 cases were assessed prospectively
between April and September 2000 as part of a separate study. The
Persian was the most frequently encountered breed and the mean age
of affected cats was 5.6 years. At initial presentation, sequestra
were unilateral in 58 cats and bilateral in 6 cats, 5 of which were
Persians. Ocular discomfort and ocular discharge were common presenting
signs, occurring in 42 and 36 eyes, respectively. Seventy-four eyes
were managed surgically with keratectomy only (n = 44) or keratectomy
followed by a graft procedure (n = 30). Sequestra recurred in 16
eyes in the study. There was no significant difference in the rate
of recurrence between eyes that received a graft procedure (n =
5) and eyes that did not (n = 11) (P = 0.56). Complications following
transection of conjunctival pedicle grafts were observed. Brown
to black discoloration of noncorneal tissue and therapeutic biomaterials
was observed, including discoloration of both viable and apparently
nonviable grafted conjunctival tissue, small intestinal submucosa
graft material and bandage contact lenses.
Craniofacial malformation - see also mucolipidosis II
Burmese kittens
The cranial cavity is enlarged, cerebral hemispheres duplicated, eyes missing or small, there may be no nostrils or naval cavities.
Anon. 1982. Craniofacial malformation in Burmese kittens. Feline Practice. 12 6 32-33
Dermatosparaxis - see Ehlers-Danlos syndrome
See article on heredity of this by Roy Robinson.
Burmese, domestic
Rand
J. 1999 Current understanding of feline diabetes: part 1, pathogenesis.J
Feline Med Surg. 1(3):143-53.
Type-1 diabetes, resulting from immune-mediated destruction of beta cells, appears to be rare in cats. Type-2 diabetes, characterised by inadequate insulin secretion and impaired insulin action, is the most common form of diabetes in cats. Other specific forms of diabetes constitute a substantial minority of cases. The most common is pancreatic destruction from pancreatic adenocarcinoma. Less frequent causes are insulin resistance from other endocrinopathies including acromegaly. Diabetes in cats is characterised by variable loss of insulin secretory capacity and insulin resistance. Glucose toxicity, islet amyloid-deposition, and pancreatitis contribute to further loss of beta cells and failure of insulin secretion. A significant number of cats undergo remission of their diabetes, usually 1-3 months after good glycaemic control is instituted. Obesity, old age, and Burmese breed are recognised risk factors for the development of diabetes in cats.
Rand
JS, Fleeman LM, Farrow HA, Appleton DJ, Lederer R. 2004 Canine and
feline diabetes mellitus: nature or nurture? J Nutr. 134(8 Suppl):2072S-2080S.
There is evidence for the
role of genetic and environmental factors in feline and canine diabetes.
Type 2 diabetes is the most common form of diabetes in cats. Evidence
for genetic factors in feline diabetes includes the overrepresentation
of Burmese cats with diabetes. Environmental risk factors in domestic
or Burmese cats include advancing age, obesity, male gender, neutering,
drug treatment, physical inactivity, and indoor confinement. High-carbohydrate
diets increase blood glucose and insulin levels and may predispose
cats to obesity and diabetes. Low-carbohydrate, high-protein diets
may help prevent diabetes in cats at risk such as obese cats or
lean cats with underlying low insulin sensitivity. Evidence exists
for a genetic basis and altered immune response in the pathogenesis
of canine diabetes. Seasonal effects on the incidence of diagnosis
indicate that there are environmental influences on disease progression.
At least 50% of diabetic dogs have type 1 diabetes based on present
evidence of immune destruction of beta-cells. Epidemiological factors
closely match those of the latent autoimmune diabetes of adults
form of human type 1 diabetes. Extensive pancreatic damage, likely
from chronic pancreatitis, causes approximately 28% of canine diabetes
cases. Environmental factors such as feeding of high-fat diets are
potentially associated with pancreatitis and likely play a role
in the development of pancreatitis in diabetic dogs. There are no
published data showing that overt type 2 diabetes occurs in dogs
or that obesity is a risk factor for canine diabetes. Diabetes diagnosed
in a bitch during either pregnancy or diestrus is comparable to
human gestational diabetes.
Diaphragmatic hernia - see Ehlers Danlos
Most diaphragmatic hernias are traumatic in origin (usually post road accident).
References
Stork CK, Hamaide AJ, Schwedes C, Clercx
CM, Snaps FR, Balligand MH. 2003 Hemiurothorax following diaphragmatic
hernia and kidney prolapse in a cat.J Feline Med Surg. 5(2):91-6
A 3-year-old cat was presented
with increasing dyspnoea over the past four days. Unilateral pleural
effusion was diagnosed and a modified transudate was drained several
times. Surgical exploration revealed intra-thoracic prolapse of
the left kidney and partial herniation of the spleen through a dorsal,
circumferential diaphragmatic tear. Biochemical analysis of the
pleural fluid confirmed urothorax. Due to excessive fibrin deposit
on the well-vascularised kidney it was impossible to re-establish
left urinary pathways. Left-sided nephrectomy and diaphragmatic
herniorrhaphy were performed. Postoperative recovery was uneventful
and complete. This is the first report of an urothorax in veterinary
medical literature.
White JD, Tisdall PL, Norris JM, Malik R. 2003 Diaphragmatic hernia in a cat mimicking a pulmonary mass. J Feline Med Surg. (3):197-201.
A seven-year-old castrated
British shorthair cross cat was presented for coughing of five-weeks
duration. Thoracic radiographs and an unguided bronchoalveolar lavage
showed changes consistent with inflammatory airway disease. In addition,
a soft tissue density was evident in the thoracic films between
the heart and the diaphragm. Exploratory thoracotomy demonstrated
a diaphragmatic hernia, probably congenital in origin, with incarceration
of a portion of the hepatic parenchyma. The herniated portion of
liver was resected surgically and the defect in the diaphragm closed.
The cat was given a 10-day course of doxycycline post-operatively
and the cough did not recur subsequently. In retrospect, the hernia
was potentially an incidental problem, the cat's coughing being
attributable to inflammatory airway disease.
Birman.
Kittens of 8 to 10 weeks of age with slowly progressive posterior ataxia.
References:
Moreau PM, Vallat JM,
Hugon J, Leboutet MJ, Vandevelde M. 1991 Peripheral and central
distal axonopathy of suspected inherited origin in Birman cats.Acta
Neu ropathol (Berl). 82(2):143-6.
Three female cats, littermates
born from clinically normal parents, were examined at 8 to 10 weeks
of age because of a slowly progressive posterior ataxia. Another
cat from a previous litter from the same parents suffered from similar
neurological symptoms. Histopathological examination of the nervous
tissues of these animals revealed degeneration of axons and myelinopathy
in a distal distribution pattern. Both peripheral nerves and central
nervous system were involved. The central nervous system lesions
were most prominent in the lateral pyramidal tracts of the spinal
cord, the fasciculi gracili of the dorsal column in the cervical
spinal cord and the cerebellar vermian white matter. In the PNS
numerous degenerating nerve fibers were found in the sciatic nerves
but not in the spinal nerve roots. Our findings show that these
cats were suffering from a hereditary multisystem degeneration with
a distribution pattern of the lesions suggestive of a distal axonopathy.
Domestic, Siamese
Associated with lysosomal storage disease of the liver, these cats die between 1 and 4 months of age. See also gangliosidosis, Mucopolysaccharidosis, Mucopolysaccharidosis VI. Uneven litter sizes have been reported in cats infected with feline coronavirus.
Hegreberg GA, Norby DE. 1973. An inherited storage disease of cats. Fed. Proc. 32 821
Hegreberg GA, Norby DE, Hamilton MJ. 1974. Lysosomal enzyme changes in an inherited dwarfism of cats. Fed Proc. 33 598.
Devon Rex, Persian and Siamese-type
Gunn-Moore DA, Thrusfield MV. 1995 Feline dystocia:
prevalence, and association with cranial conformation and breed.Vet
Rec. 136(14):350-3.
The litter prevalence of
feline dystocia was investigated using a questionnaire survey of
cat breeders. Information was obtained on 2928 litters, from 735
queens. Dystocia was reported to have occurred in 5.8 per cent of
litters. The level of dystocia in individual breeds ranged from
0.4 per cent of litters born in a large colony of cats of mixed
breeding, to 18.2 per cent of litters in the Devon rex. Pedigree
litters were at significantly higher risk than litters of cats of
mixed breeding (odds ratio: 22.6). Relatively high levels of dystocia
were identified in Siamese-type, Persian and Devon rex litters,
whereas cats of mixed breeding showed a relatively low litter prevalence.
Dolicocephalic and brachycephalic types were found to have significantly
higher levels of dystocia than mesocephalic cats.
Cutaneous asthenia is a connective tissue disease primarily of dogs and cats, resembling Ehlers-Danlos syndrome in man. It has also been reported in a rabbit. The skin is hyperextensible, thin, and fragile.
No breed predilection recorded so far.
References
Benitah N, Matousek JL, Barnes RF, Lichtensteiger CA, Campbell KL. 2004 Diaphragmatic and perineal hernias associated with cutaneous asthenia in a cat. J Am Vet Med Assoc. Mar 1;224(5):706-9, 698.
An 11-year-old cat was evaluated
because of dyspnea. Since 11 months of age, the cat had hyperextensibility
of the skin consistent with cutaneous asthenia. Radiographic examination
revealed a diaphragmatic hernia with intestinal loops in the thorax.
Electron microscopic examination of skin specimens revealed collagen
fibers of highly variable diameter, consistent with cutaneous asthenia.
The diaphragmatic
hernia was surgically repaired and healed well. Four weeks later,
a left-sided perineal hernia was repaired surgically, and 4 months
later, a right-sided perineal hernia was repaired surgically and
colopexy and cystopexy were performed. All surgical procedures were
successful and tissues healed well. Dermatosparaxis is a rare hereditary
disorder that commonly results in cutaneous fragility and hyperextensibility
in affected animals. The diagnosis depends on clinical findings
and light and electron microscopic changes in affected tissues.
Surgical repair can be performed successfully in an affected cat,
and healing of incisions can occur without complications.
Freeman
LJ, Hegreberg GA, Robinette JD, Kimbrell JT. 1989 Biomechanical
properties of skin and wounds in Ehlers-Danlos syndrome.Vet Surg.
8(2):97-102.
The biomechanical properties
of wounded and nonwounded skin were studied in three dogs and three
cats affected with type I Ehlers-Danlos syndrome. Three nonaffected
dogs and one nonaffected cat served as controls. Samples of wounded
skin and adjacent normal skin were harvested at days 75, 138, 141,
144, 147, and 150. Samples were subjected to uniaxial tensile strength
testing. Tensile strength, energy absorbed, and site of failure
were recorded. In the dogs with Ehlers-Danlos syndrome, there was
an increase in tensile strength in samples containing a scar over
adjacent intact skin. In nonaffected dogs, affected cats and the
nonaffected cat, the nonwounded skin samples had greater tensile
strength. The energy absorbed by the skin samples during testing
was highly correlated with tensile strength.
Freeman
LJ, Hegreberg GA, Robinette JD. 1989 Cutaneous wound healing in
Ehlers-Danlos syndrome.Vet Surg. 18(2):88-96.
Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs, affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had dehiscence of all or part of the incision line and healed by granulation, contraction, and epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to determine if there were any differences in rates of healing between affected and nonaffected animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75, incision sites were recognized by fine, more compact collagen bundles and lack of adnexal structures, as compared with the adjacent dermis in both affected and nonaffected animals. Although delayed wound healing has been reported to be a complication of Ehlers-Danlos syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with Ehlers-Danlos syndrome appears to be similar to nonaffected animals.
Birman
Onset 2-5 months of age. Hindlimb paresis and ataxia, which progresses to paralysis. Bilateral nuclear cataracts may be present. Condition is inherited. Histopathology: spongy changes, vacuolation and wallerian degeneration, mainly in thoracolumbar spinal cord. Diffuse lesions also present in brain. No treatment.
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
Feline infectious peritonitis - predisposition to development of
Feline leukocyte antigen restricted polymorphism
Siamese
Feline infectious peritonitis - predisposition to development of
Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes are MORE at risk
Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats are NOT AT INCREASED risk for development of FIP.
References
Pesteanu-Somogyi LD, Radzai C, Pressler BM. 2005 Prevalence of feline infectious
peritonitis in specific cat breeds. J Feline Med Surg.
Although known that purebreed
cats are more likely to develop feline infectious peritonitis (FIP),
previous studies have not examined the prevalence of disease in
individual breeds. All cats diagnosed with FIP at a veterinary teaching
hospital over a 16-year period were identified. Breed, sex and reproductive
status of affected cats were compared to the general cat population
and to mixed breed cats evaluated during the same period. As with
previous studies sexually intact cats and purebreed cats were significantly
more likely to be diagnosed with FIP; males and young cats also
had a higher prevalence of disease. Abyssinians, Bengals, Birmans,
Himalayans, Ragdolls and Rexes had a significantly higher risk,
whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues
and Siamese cats were not at increased risk for development of FIP.
Although additional factors doubtlessly influence the relative prevalence
of FIP, this study provides additional guidance when prioritizing
differentials in ill purebreed cats.
Feline leukocyte antigen DRB restricted polymorphism
Burmese
Reference
Kennedy
LJ, Ryvar R, Brown JJ, Ollier WE, Radford AD.Resolution of complex
feline leukocyte antigen DRB loci by reference strand-mediated conformational
analysis (RSCA). Tissue Antigens. 2003 Oct;62(4):313-23.
The DRB genes of the domestic cat are highly polymorphic. Studies based on clonal sequence analysis have suggested the existence of two distinct loci within individual animals and good evidence for 24 distinct FLA-DRB alleles. This variability, the complexity of clonal sequence analysis and its susceptibility to PCR-induced artefacts has represented a bottleneck to further progress. In this study we have applied reference strand-mediated conformational analysis (RSCA) to FLA-DRB. This protocol has been shown to be highly reproducible. Using five reference strands including two derived from non-domestic felines, we could distinguish 23 FLA-DRB alleles. We used RSCA to explore genetic polymorphism of FLA-DRB in 71 cats including 31 for which clonal sequence analysis was also available. On average, RSCA identified 0.9 more alleles within cats than clonal sequence analysis. Reference strand-mediated conformational analysis was also able to identify animals containing new alleles that could be targeted for sequence analysis. Analysis of allele patterns showed clear evidence for different allele distributions between breeds of cats, and suggested the Burmese breed may have highly restricted FLA-DRB polymorphism. Results from two families provided clear evidence for variation in the number of DRB genes on different haplotypes, with some haplotypes carrying two genes and some containing three. This study highlights the utility of RSCA for the resolution of complex amplicons containing up to six distinct alleles. A simple, rapid method for characterizing FLA-DRB makes possible studies on vaccine response and susceptibility/resistance to viral infections, which are a significant clinical problem in cats.
Burmese
Gingivitis - hyperplastic, early onset
Domestic shorthair, Korat
Clinical signs: slowly progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Circulating monocytes and lymphocytes showed the presence of single or multiple empty vacuoles.
Mode of inheritance: autosomal, recessively inherited.
GM1 gangliosidosis
References
Cox
NR, Morrison NE, Sartin JL, Buonomo FC, Steele B, Baker HJ. 1999
Alterations in the growth hormone/insulin-like growth factor I pathways
in feline GM1 gangliosidosis.Endocrinology. 140(12):5698-704.
Cats affected with feline
GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal
enzymopathy, have progressive neurological dysfunction, premature
thymic involution, stunted growth, and premature death. Although
increased membrane GM1 gangliosides can result in increased apoptosis
of thymocytes, there is not a direct correlation between thymocyte
surface GM1 and thymic apoptosis in vivo, suggesting that other
factors may be important to the pathogenesis of thymic involution
in affected cats. Because GH and insulin-like growth factor I (IGF-I)
are important hormonal peptides supporting thymic function and affecting
growth throughout the body, particularly in the prepubescent period,
several components of the GH/IGF-I pathway were compared in GM1
mutant and normal age-matched cats. GM1 mutant cat serum IGF-I concentrations
were reduced significantly compared with those in normal cats by
150 days of age, and GM1 mutant cats had no peripubertal increase
in serum IGF-I. Additionally, IGF-binding protein-3 was reduced,
and IGF-binding protein-2 was elevated significantly in GM1 mutant
cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary
GH messenger RNA both were reduced significantly in GM1 mutant cats.
After stimulation by exogenous recombinant canine GH, serum IGF-I
levels increased significantly in GM1 mutant cats, indicating that
GH/IGF-I signaling pathways within the liver remain intact and suggesting
that alterations are external to the liver.
De Maria R,
Divari S, Bo S, Sonnio S, Lotti D, Capucchio MT, Castagnaro M. 1998
Beta-galactosidase deficiency in a Korat cat: a new form of feline
GM1-gangliosidosis.Acta Neuropathol (Berl). 96(3):307-14.
A 7-month-old Korat cat was
referred for a slowly progressive neurological disease. Circulating
monocytes and lymphocytes showed the presence of single or multiple
empty vacuoles and blood leukocytes enzyme assay revealed a very
low beta-galactosidase activity level (4.7 nmol/mg per h) as compared
to unaffected parents and relatives. Histologically, the cat, euthanized
at the owner request at 21 months of age, presented diffuse vacuolization
and enlargement of neurons throughout the brain, spinal cord and
peripheral ganglia, severe cerebellar neuronal cell loss, and moderate
astrocytosis. Stored material was stained with periodic acid-Schiff
on frozen sections and with the lectins Ricinus conmmunis agglutinin-I,
concanavalin A and wheat germ agglutinin on paraffin-embedded sections.
Ultrastructurally, neuronal vacuoles were filled with concentrically
whorled lamellae and small membrane-bound vesicles. In the affected
cat, beta-galactosidase activity was markedly reduced in brain (18.9%)
and liver (33.25%), while total beta-hexosaminidase activity showed
a remarkable increase. Quantitation of total gangliosides revealed
a 3-fold increase in brain and 1.7-fold in liver of affected cat.
High-performance thin layer chromatography (HPTLC) detected a striking
increase of GM1-ganglioside. On densitometric analysis of HPTLC
bands, the absorption of GM1-ganglioside band was 98.52% of all
stained bands (GD1a, GD1b, GT1b). Based on clinical onset, morphological
and histochemical features, and biochemical findings, the Korat
cat GM1-gangliosidosis is comparable with the human type II (juvenile)
form. However, clinical progression, survival time and level of
beta-galactosidase deficiency do not completely fit with those of
human type II GM1-gangliosidosis. The disease in the Korat cat is
also different from other reported forms of feline GM1-gangliosidosis.
Steiss
JE, Baker HJ, Braund KG, Cox NR, Wright JC.1997 Profile of electrodiagnostic
abnormalities in cats with GM1 gangliosidosis.Am J Vet Res. 58(7):706-9.
OBJECTIVE: To determine which
electrodiagnostic tests yield abnormal findings in cats with GM1
gangliosidosis, and to determine the approximate age of onset of
electrodiagnostic abnormalities. ANIMALS: Cats (28 to 335 days old)
affected with GM1 gangliosidosis (n = 11) and unaffected controls
(n = 14). PROCEDURE: Cats were grouped by age: group 1, < or
= 90 days, group 2, 91 to 200 days; and group 3, > 200 days.
Electrodiagnostic tests were conducted, including needle electromyography,
motor and sensory nerve conduction velocity, spinal evoked potentials,
and brainstem auditory evoked potentials. Results for control and
affected cats were compared, using the general linear model for
ANOVA and Scheffe's test for multiple comparisons. RESULTS: Needle
electromyography did not reveal abnormal spontaneous activity in
skeletal muscles of any cat; furthermore, statistical analysis did
not indicate significant difference between affected and control
groups for nerve conduction velocity, confirming that degeneration
of peripheral nerve fibers is not a feature of this disease. However,
spinal evoked potentials were abnormal in group-3 cats; conduction
velocity within sensory pathways in the cranial part of the spinal
cord was significantly slower in GM1-affected cats (P = 0.0002).
Brainstem auditory evoked responses also were abnormal: wave V (generated
in the region of the pons) had prolonged latency in cats of groups
2 and 3 (P = 0.0003 and 0.0001, respectively, at 90 decibels sound
pressure level). In the oldest cats, latencies for earlier waves
within the auditory pathway also were prolonged; wave I (generated
by the cochlear nerve) was prolonged in group-3 cats (P = 0.0423).
CONCLUSIONS: Motor and sensory nerve conduction velocities remained
within normal limits in GM1-affected cats. However, spinal evoked
potentials indicated slowing in conduction velocity along the cranial
part of the spinal cord in group 3 cats. Brainstem auditory evoked
responses indicated prolonged latencies in cats of groups 2 and
3.
GM2 gangliosidosis
Martin
DR, Krum BK, Varadarajan GS, Hathcock TL, Smith BF, Baker HJ.2004
An inversion of 25 base pairs causes feline GM2 gangliosidosis variant.Exp
Neurol. 187(1):30-7.
In G(M2) gangliosidosis variant
0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase
(EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside
and severe neurodegeneration. Distinct feline models of G(M2) gangliosidosis
variant 0 have been described in both domestic shorthair and Korat
cats. In this study, we determined that the causative mutation of
G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair
inversion at the extreme 3' end of the beta-subunit (HEXB) coding
sequence, which introduces three amino acid substitutions at the
carboxyl terminus of the protein and a translational stop that is
eight amino acids premature. Cats homozygous for the 25-base-pair
inversion express levels of beta-subunit mRNA approximately 190%
of normal and protein levels only 10-20% of normal. Because the
25-base-pair inversion is similar to mutations in the terminal exon
of human HEXB, the domestic shorthair cat should serve as an appropriate
model to study the molecular pathogenesis of human G(M2) gangliosidosis
variant 0 (Sandhoff disease).
Muldoon
LL, Neuwelt EA, Pagel MA, Weiss DL. 1994 Characterization of the
molecular defect in a feline model for type II GM2-gangliosidosis
(Sandhoff disease).Am J Pathol. 144(5):1109-18.
The Korat cat provides an
animal model for type II GM2-gangliosidosis (Sandhoff disease) that
may be suitable for tests of gene replacement therapy with the HEXB
gene encoding the beta subunit of the beta-hexosaminidases. In the
present report, we examined the brain and liver pathology of a typical
Sandhoff-affected cat. We characterized the feline HEXB complementary
DNA (cDNA) and determined the molecular defect in this feline model.
cDNA libraries were produced from one normal and one affected animal,
and cDNA clones homologous to human HEXB were sequenced. In the
affected cDNA clone, the deletion of a cytosine residue at position
+39 of the putative coding region results in a frame shift and a
stop codon at base +191. This disease-related deletion was consistently
detected by sequencing of cloned polymerase chain reaction amplified
reverse transcribed messenger RNA from one more normal Korat and
two additional affected animals. The defect was further demonstrated
using single-strand conformational polymorphism analysis of the
polymerase chain reaction products. In addition, alternative splicing
of both normal and affected messenger RNAs was demonstrated. These
results should facilitate the use of this animal model to assess
gene therapy.
Yamato
O, Matsunaga S, Takata K, Uetsuka K, Satoh H, Shoda T, Baba Y, Yasoshima
A, Kato K, Takahashi K, Yamasaki M, Nakayama H, Doi K, Maede Y,
Ogawa H.GM2-gangliosidosis variant 0 (Sandhoff-like disease) in
a family of Japanese domestic cats.Vet Rec. 2004 Dec 4;155(23):739-44.
Erratum in: Vet Rec. 2005 Jan 15;156(3):86.
A five-month-old, female
Japanese domestic shorthair cat with proportionate dwarfism developed
neurological disorders, including ataxia, decreased postural responses
and generalised body and head tremors, at between two and five months
of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic
vacuolations was observed. The concentration of G(M2)-ganglioside
in its cerebrospinal fluid was markedly higher than in normal cats,
and the activities of beta-hexosaminidases A and B in its leucocytes
were markedly reduced. On the basis of these biochemical data, the
cat was diagnosed antemortem with G(M2)-gangliosidosis variant 0
(Sandhoff-like disease). The neurological signs became more severe
and the cat died at 10 months of age. Histopathologically, neurons
throughout the central nervous system were distended, and an ultrastructural
study revealed membranous cytoplasmic bodies in these distended
neurons. The compound which accumulated in the brain was identified
as G(M2)-ganglioside, confirming G(M2)-gangliosidosis. A family
study revealed that there were probable heterozygous carriers in
which the activities of leucocyte beta-hexosaminidases A and B were
less than half the normal value. The Sandhoff-like disease observed
in this family of Japanese domestic cats is the first occurrence
reported in Japan.
Burmese
References
Hampson EC, Smith RI,
Bernays ME. 2002 Primary glaucoma in Burmese cats.Aust Vet J. 80(11):672-80.
OBJECTIVE: To document the
clinical signs and management of primary glaucoma in Burmese cats.
DESIGN: A retrospective study of six affected Burmese cats, from
1996 to 2001. Procedure Six Burmese cats diagnosed with primary
glaucoma were managed over periods varying from 3 months to 4.5
years. Clinical details were obtained from practice records. Gonioscopic
examination of the drainage or iridocorneal angle in eyes of these
affected cats was made. RESULTS: Six desexed female Burmese cats
(ages 7.0 to 10.5 years) presented with complaints of either unilateral
(n = 4) or bilateral (n = 2) red eye, dilated pupil or enlarged
eye. In one of the affected cats, one eye had been enucleated prior
to the commencement of the study, thus a total of 11 eyes were examined.
Clinically, all affected eyes (n = 8) had injected episcleral blood
vessels and elevated intraocular pressure. Gonioscopy revealed the
presence of nine narrow and two closed iridocorneal angles. Medical
therapy included topical 2% dorzolamide (n = 8), 0.5% timolol maleate
(n = 1), 0.005% latanoprost (n = 1) and 0.5-1.0% prednisolone acetate
(n = 8). Surgery was performed in six eyes using either diode laser
(n = 5) and/or cryothermy (n = 2) and one eye was eviscerated, with
implantation of a prosthesis. With therapy, five affected eyes maintained
vision and normal intraocular pressure, one eye remained blind with
normal intraocular pressure, one eye remained blind with elevated
intraocular pressure and one eye was eviscerated. CONCLUSIONS: The
Burmese cat may be predisposed to primary narrow-angle glaucoma.
Early diagnosis and continuous antiglaucoma therapy can help control
intraocular pressure and maintain vision.
Gingivitis - hyperplastic, early-onset
Abysinnian, Persian
Clinical signs: hyperemic, proliferative gingivitis
Gingivitis-periodontitis - feline juvenile-onset
DSH, Maine Coon, Siamese
Small stature and have a history of being "sickly" as kittens, often with chronic upper respiratory disease. Initial oral signs occur just before eruption of adult teeth. Gingival recession, pocketing, bone loss and furcation exposures are common. Lesions may be localized or generalized and often first seen in the central lower incisor area.
Reference
Williams CA, Aller MS. 1992 Gingivitis/stomatitis in cats. Veterinary Clinics of North America. 22 6 1361 - 1383
Type IV glycogen storage disease
Norwegian Forest Cats
Reference
Fyfe JC,
Giger U, Van Winkle TJ, Haskins ME, Steinberg SA, Wang P, Patterson
DF.1992 Glycogen storage disease type IV: inherited deficiency of
branching enzyme activity in cats.Pediatr Res.32(6):719-25.
Glycogen storage disease
type IV due to branching enzyme deficiency was found in an inbred
family of Norwegian forest cats, an uncommon breed of domestic cats.
Skeletal muscle, heart, and CNS degeneration were clinically apparent
and histologically evident in affected cats older than 5 mo of age,
but cirrhosis and hepatic failure, hallmarks of the human disorder,
were absent. Beginning at or before birth, affected cats accumulated
an abnormal glycogen in many tissues that was determined by histochemical,
enzymatic, and spectral analysis to be a poorly branched alpha-1,4-D-glucan.
Branching enzyme activity was less than 0.1 of normal in liver and
muscle of affected cats and partially deficient (0.17-0.75 of normal)
in muscle and leukocytes of the parents of affected cats. These
data and pedigree analysis indicate that branching enzyme deficiency
is a simple autosomal recessive trait in this family. This is the
first reported animal model of human glycogen storage disease type
IV. A breeding colony derived from a relative of the affected cats
has been established.
Hemophilia A (factor VIII deficiency)
Haemophilia B - factor IX deficiency - Christmas disease
Hageman (coagulation factor XII) deficiency
Heart defect - see Ventricular Septal Defect
Haemophilia B - factor IX deficiency - Christmas disease
British shorthair, Domestic
Clinical signs: regenerative anaemia, haemorrhage, subcutaneous haematomas, prolonged bleeding times, shifting lameness.
References
Dillon AR, Boudreaux MK. 1988 Combined factors IX and XII deficiencies in a family of cats.J Am Vet Med Assoc. 193(7):833-4.
Combined factors IX and XII
deficiencies were detected in a family of cats in which 2 male kittens
had bleeding diathesis. The combination of factors IX and XII deficiencies
in one male kitten did not appear to exacerbate bleeding when compared
with a sole deficiency of factor IX in its male sibling. Neutering
of carrier females and affected males was recommended. Blood transfusions
before castration of affected males was advised.
Goree M,
Catalfamo JL, Aber S, Boudreaux MK. 2005 Characterization of the
mutations causing hemophilia B in 2 domestic cats.J Vet Intern Med.
2005 Mar-Apr;19(2):200-4.
The purpose of the present study was to determine the normal sequence for the gene encoding factor IX in cats and to characterize the genetic basis for hemophilia B in 2 unrelated male, domestic, mixed-breed cats. Genomic DNA sequence for the entire coding region of the factor IX gene was determined in the affected cats and compared to the sequence obtained from a healthy cat. The factor IX gene in cats encodes a mature protein consisting of 420 amino acids, unlike genes in humans and dogs that encode 415 and 413 amino acid proteins, respectively. Affected cat 1 had a single nucleotide change in exon 8 at the 1st nucleotide position of the codon encoding an arginine (CGA to TGA) at amino acid position 338. This mutation would be predicted to result in the appearance of a premature stop codon in the portion of the gene encoding much of the catalytic domain of the protein. Affected cat 2 had a single nucleotide change in exon 4 at the 2nd nucleotide position of the codon encoding amino acid 82 (TGT to TAT), which would be predicted to result in the substitution of a tyrosine for a cysteine. This substitution would likely result in disruption of a disulfide bond crucial to normal protein structure and function. This study represents the 1st time hemophilia B has been characterized at the molecular level in cats.
Lutze G, Kutschmann K, Furst K, Schneppenheim R. 2005 Hemophilia B (factor IX deficiency) with concomitant factor XII degradation in a male crossbreed cat. Berl Munch Tierarztl Wochenschr. 118(5-6):255-60.
A male cat suffered from a severe haemorrhagic disorder manifesting as deep, partly infected cutaneous haematomas, enhanced and prolonged bleeding after injuries and subsequent lameness at several occasions. Bleeding resulted in severe anaemia with haematocrit falling to as low as 0.10 L/L. Haemophilia B was diagnosed based on factor IX deficiency with a functional residual activity of 5% and factor IX antigen of 8%, respectively. Additionally, factor XII activity was reduced to 32% of normal. The mutation 31217G==>A in exon 8 of the factor IX gene, predicting the amino acid exchange G366R was identified as the cause of moderate factor IX deficiency. This is the first mutation identified in cats with haemophilia B. Treatment was limited to local therapy and palliation, insufficient to prevent lethal outcome due to severe anaemia.
Maggio-Price L, Dodds WJ. 1993 Factor IX deficiency (hemophilia B) in a family of British shorthair cats.J Am Vet Med Assoc. 203(12):1702-4.
This report describes the
clinical findings of a British shorthair cat with hemophilia B,
the family pedigree surrounding the case, and how this disorder
can be perpetuated in rare breeds of cats that may be inbred by
necessity. Young cats with histories of bleeding episodes following
elective or other surgical procedures, periodic shifting lamenesses,
or the development of subcutaneous hematomas should be suspect for
an inherited coagulation disorder. Hemophilia A (factor VIII deficiency)
or hemophilia B (factor IX deficiency) are the most likely causes,
although other inherited bleeding disorders also have been recognized
in cats.
Hageman (coagulation factor XII) deficiency
Domestic
Mode of inheritance: autosomal recessive
References
Dillon AR, Boudreaux MK. 1988 Combined factors IX and XII deficiencies in a family of cats.J Am Vet Med Assoc. 193(7):833-4.
Combined factors IX and XII deficiencies were detected in a family of cats in which 2 male kittens had bleeding diathesis. The combination of factors IX and XII deficiencies in one male kitten did not appear to exacerbate bleeding when compared with a sole deficiency of factor IX in its male sibling. Neutering of carrier females and affected males was recommended. Blood transfusions before castration of affected males was advised.
Kier AB,
Bresnahan JF, White FJ, Wagner JE. The inheritance pattern of factor
XII (Hageman) deficiency in domestic cats.Can J Comp Med. 1980 Jul;44(3):309-14.
Measurements of coagulation factor XII levels in F1 progeny of a cat having factor XII deficiency revealed an autosomal recessive pattern similar to that reported in humans (Hageman trait). A study of the pedigree of the colony revealed that F1 kittens had approximately 50% factor XII activity while kittens produced by backcrossing with an F1 progeny possessed an average of 50% and a less than 2% factor XII activity in an approximate 1:1 ratio. Kittens having an average of 50% factor XII activity were postulated heterozygous for the trait while progeny with less than 2% activity were considered genetically homozygous.
Hernia - hernias can be secondary to Ehlers-Danlos syndrome
Hiatus hernia
Perineal hernia
Umbillical hernia
Clinical signs: hindlimb lameness, history of constipation
References
Keller
GG, Reed AL, Lattimer JC, Corley EA. 1999 Hip dysplasia: a feline
population study.Vet Radiol Ultrasound. 40(5):460-4.
The study population consisted
of cats presented to the University of Missouri-Columbia Veterinary
Medical Teaching Hospital from January 1, 1991 through December
31, 1995. Ventrodorsal radiographs including the pelvic region were
evaluated for radiographic evidence of hip dysplasia. Each radiograph
was evaluated independently by three board-certified veterinary
radiologists and a consensus normal of dysplastic evaluation was
determined. There were 684 cats from 12 breeds. The data derived
from this study indicate the frequency of feline hip dysplasia in
this population to be about 6.6% (45/684) and that the incidence
appears to be breed dependent. Also, the radiographic appearance
of hip dysplasia in cats is different than in dogs. A shallow acetabulum
with remodeling and proliferation involving the cranio-dorsal acetabular
margin were the most common radiographic signs. Minimal remodeling
of the femoral neck was seen.
Patsikas MN, Papazoglou LG, Komninou A, Dessiris AK, Tsimopoulos G. 1998 Hip dysplasia in the cat: a report of three cases. J Small Anim Pract. 39(6):290-4.
Hip dysplasia was diagnosed in three cats. Two were presented with a history of hindlimb lameness and the other had a history of constipation. All were confined for two weeks and showed considerable clinical improvement. At follow-up examination the cats were free of clinical signs despite the deterioration in the radiological appearance of their hips. Luxation or subluxation of the hips, insufficient development of the craniolateral acetabular edges, loss of the arched shape of the cranial subchondral acetabular bones, shallow acetabula and secondary degenerative changes on the femoral heads and necks were the main radiological findings in the affected cats.
Breeds: Maine Coon, Ragdoll
Clinical signs: sudden death, thickened wall of left ventricle on echocardiography
Mode of inheritance:
References
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.
Burmese
Clinical signs: periodic muscle weakness and cervical ventroflexion, onset can be as early as 10 weeks old.
Mode of inheritance: homozygote recessive
References
Gaschen F, Jaggy A, Jones B. 2004 Congenital diseases of feline muscle and neuromuscular junction. J Feline Med Surg. (6):355-66.
Although muscle diseases
occur relatively rarely in cats, a number of congenital feline myopathies
have been described over the last 20 years and are reviewed in this
paper. Some of them have been reported exclusively in specific breeds,
including the hypokalaemic myopathy of Burmese cats, type IV glycogen
storage disease in Norwegian Forest cats, or the myopathy of Devon
Rex. Other congenital disorders of muscle and neuromuscular junction
such as myotonia congenita, dystrophin-deficient hypertrophic feline
muscular dystrophy, laminin alpha2 deficiency, or congenital myasthenia
gravis may occur in any cat. A systematic approach is essential
in order to efficiently obtain a timely diagnosis in cats showing
signs of muscle disease. After a thorough clinical examination,
this approach includes blood analyses (eg, serum concentration of
muscle enzymes), electrophysiology where available (electromyography,
nerve conduction studies), and sampling of muscle biopsies for histological,
histochemical and immunohistochemical evaluation. When available,
detection of healthy carriers of these genetic disorders is important
to eliminate the gene mutations from breeding families. Clinicians
regularly receiving feline patients must have a good knowledge of
congenital feline myopathies and the features which enable a diagnosis
to be made and prognosis given. Besides preserving or restoring
the well-being of the myopathic patient, rapid and efficient information
and counselling of the breeders are of central importance in order
to prevent the recurrence of the problem in specific breeding lines.
Jones BR, Swinney GW, Alley MR. 1988 Hypokalaemic myopathy in Burmese kittens.N Z Vet J. 36(3):150-1.
Since 1984 there have been
a number of reports of polymyopathy in cats characterised by clinical
signs of generalised weakness of the limb and neck muscles. In most
of these cases the polymyopathy was associated with a concurrent
hypokalaemia. A direct causal relationship was not established in
one series of cases, but in the second excessive urine potassium
loss with decreased potassium intake was suspected. It was concluded
by these authors that increased urinary potassium secretion was
a basic response to renal dysfunction in cats. Periodic muscle weakness
has also been recognised in young Burmese kittens (10 weeks to one
year) which was characterised by ventroflexion of the neck, elevated
creatinine phosphokinase (CPK) activity and intermittent hypokalaemia.
Lantinga
E, Kooistra HS, van Nes JJ. 1998 Periodic muscle weakness and cervical
ventroflexion caused by hypokalemia in a Burmese cat. Tijdschr Diergeneeskd.
123(14-15):435-7.
A 2-year-old female Burmese
cat was referred to the University Hospital of Companion Animals
of Utrecht University because of periodic muscle weakness and cervical
ventroflexion. Laboratory examinations revealed hypokalemia. The
combination of breed, clinical signs and hypokalemia warranted the
diagnosis of 'periodic hypokalemic myopathy', a homozygote recessive
hereditary disease in Burmese cats. Potassium supplementation resulted
in complete disappearance of the signs. Possible causes of hypokalemia
in the cat are discussed.
Laminin alpha2 deficiency - see muscular dystrophy
Lipoprotein lipase deficiency - congenital
Lipoprotein lipase deficiency - congenital
Clinical signs: fasting hyperlipaemia, lipaemia retinalis, peripheral neuropathies and subcutaneous xanthomas
References
Johnstone
AC, Jones BR, Thompson JC, Hancock WS. 1990 The pathology of an
inherited hyperlipoproteinaemia of cats. J Comp Pathol. 102(2):125-37
The gross and histological features of congenital lipoprotein lipase deficiency are described in eight cats. The main histological features could be directly related to the presence of the chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques. Focal degenerative changes were, however, present within arteries and this may indicate blood vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises from pressure necrosis of adjacent xanthomata and alterations in renal blood flow.
Jones BR, Wallace A, Harding DR, Hancock WS, Campbell CH 1983.Occurrence of idiopathic, familial hyperchylomicronaemia in a cat. Vet Rec. 112(23):543-7.
Primary hyperlipoproteinaemia (hyperchylomicronaemia with slight very low density lipoprotein elevation) is described in two related male cats. Fasting hyperlipaemia, lipaemia retinalis and subcutaneous xanthomas were detected on clinical examination. In one cat lipoprotein lipase activity measured after heparin activation was significantly reduced compared to the response in a normal cat. The lipid and protein concentration in each of the lipoprotein classes and the lipoprotein distribution of the two hyperlipaemic cats, two normolipaemic relations and 16 normolipaemic adult cats were determined. Plasma cholesterol and triglyceride levels were elevated in the hyperlipaemic cats with the major proportion of triglyceride and cholesterol being present in chylomicrons whereas in normolipaemic cats the majority of triglyceride was contained in very low density lipoprotein. High density lipoprotein was the predominant lipid carrier in both the normolipaemic and the hyperlipaemic cats but the protein content in chylomicrons was elevated in the two affected cats. The lipoprotein distribution in normal cats in this study agrees with previously reported values. The hyperlipaemic cats showed many of the features of familial lipoprotein lipase deficiency (type I hyperlipoproteinaemia, exogenous chylomicronaemia) which is an inherited disease in man.
Jones BR, Johnstone AC, Cahill JI, Hancock WS. 1986 Peripheral neuropathy in cats with inherited primary hyperchylomicronaemia.Vet Rec. 1986 Sep 13;119(11):268-72.
Primary hyperlipoproteinaemia
(hyperchylomicronaemia) with a slight increase in very low density
lipoprotein) is described in 20 cats. Fasting hyperlipaemia, lipaemia
retinalis and peripheral neuropathies were the most frequently detected
clinical signs. The disease is thought to be inherited as an autosomal
recessive trait but the exact mode of inheritance has not been determined.
Affected cats showed reduced lipoprotein lipase activity measured
after heparin activation compared with the response in normal cats.
Plasma triglyceride and cholesterol were increased in all the cats
with the major proportion of triglyceride and cholesterol being
present in chylomicrons. The peripheral nerve lesions were caused
by compression of nerves by lipid granulomata. It is probable that
the lipid granulomata result from trauma because the nerves most
often affected were at sites like the spinal foraminae where they
were susceptible to trauma.
Thompson JC, Johnstone AC, Jones BR, Hancock
WS. 1989 The ultrastructural pathology of five lipoprotein lipase-deficient
cats.J Comp Pathol. 101(3):251-62.
The ultrastructural pathology of cats suffering from familial lipoprotein lipase deficiency is described. There were large numbers of lipid vacuoles within hepatocytes, epithelial cells of the proximal convoluted tubule of kidney and macrophages of the liver, spleen and lymph node. The older cats tended to have larger quantities of ceroid within hepatocytes and macrophages, and all stages of development of ceroid were observed. Chylomicron emboli were seen within the glomerular capillaries and interlobular blood vessels. There was podocyte foot fusion and thickening of basement membranes of glomeruli, Bowman's capsule and some proximal convoluted tubules, similar to that seen in diabetes mellitus. These changes represent a non-specific reaction of the kidney to noxious insults such as hypoxia caused by emboli. Transformation of smooth muscle cells from a contractile to a synthetic state was seen in the splenic trabeculae and, to a lesser extent, in blood vessels. Dilatations of the nuclear membrane of the lymphocytes were noted, the significance of which is unknown.
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.
Robinson
R. 1993 Expressivity of the Manx gene in cats. J Hered. 1993 May-Jun;84(3):170-2.
New genetic data are presented
which indicate that the assortment data for the mutant Manx gene,
M, does not depart from normal expectation and does not enjoy a
selective advantage at some stage of gametogenesis, as has been
hypothesized. The variable expression of Manx taillessness is a
remarkable and consistent feature of the Manx syndrome, encompassing
the posterior skeleton, neural organization, and growth of soft
tissues. The expression is partly genetic in origin, and the heritability
is estimated to be in the region of h2 = 0.40 +/- 0.11.
Domestic
Clinical signs: clinical features in affected kittens were observed from birth in some kittens, others are months old when presented. Clinical signs include failure to thrive, abnormal facial features, retarded growth, behavioral dullness, facial dysmorphia, diffuse retinal degeneration leading to blindness by 4 months of age, ataxia, progressive hindlimb paresis, upper respiratory signs, cardiac failure. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion.
Mode of inheritance: autosomal recessive
References
Hubler M, Haskins ME, Arnold S, Kaser-Hotz B, Bosshard NU, Briner J, Spycher MA, Gitzelmann R, Sommerlade HJ, von Figura K. 1996 Mucolipidosis type II in a domestic shorthair cat. J Small Anim Pract. 1996 Sep;37(9):435-41.
A seven-month-old, female
domestic shorthair cat was presented to the Veterinary Teaching
Hospital, University of Zurich, with abnormal facial features, retarded
growth and progressive hindlimb paresis. On physical examination
the cat had a flat, broad face with hypertelorism, frontal bossing,
small ears and thickened upper and lower eyelids. The corneas of
both eyes were clear and the pupils were dilated. The skin was generally
thickened, most prominently on the dorsal aspect of the neck. Radiography
of the entire skeleton revealed a severely deformed spinal column,
bilateral hip luxation with hip dysplasia, an abnormally shaped
skull and generalised decreased bone opacity. The clinical features
and radiographic changes were suggestive of mucopolysaccharidosis.
The toluidine blue spot test on a urine sample, however, was negative
for glycosaminoglycans. Further biochemical investigations revealed
a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase
(GlcNAc-phosphotransferase, EC 2.7.8.17) in peripheral leukocytes
and an elevation of many lysosomal enzymes in the serum of the cat
which is diagnostic for mucolipidosis type II. Histology and electron
microscopy of different tissues are briefly summarised. The findings
of this cat, the first reported case of mucolipidosis type II are
compared with other similar storage diseases described in the cat.
Mazrier H, Van Hoeven M, Wang P, Knox VW, Aguirre GD, Holt E, Wiemelt SP, Sleeper MM, Hubler M, Haskins ME, Giger U. 2003 Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease. J Hered. 94(5):363-73.
Mucolipidosis II (ML II),
also called I-cell disease, is a unique lysosomal storage disease
caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase,
which leads to a failure to internalize enzymes into lysosomes.
We report on a colony of domestic shorthair cats with ML II that
was established from a half-sibling male of an affected cat. Ten
male and 9 female kittens out of 89 kittens in 26 litters born to
clinically normal parents were affected; this is consistent with
an autosomal recessive mode of inheritance. The activities of three
lysosomal enzymes from affected kittens, compared to normal adult
control cats, were high in serum (11-73 times normal) but low in
cultured fibroblasts (9-56% of normal range) that contained inclusion
bodies (I-cells), reflecting the unique enzyme defect in ML II.
Serum lysosomal enzyme activities of adult obligate carriers were
intermediate between normal and affected values. Clinical features
in affected kittens were observed from birth and included failure
to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic
lesions included metaphyseal flaring, radial bowing, joint laxity,
and vertebral fusion. In contrast to human ML II, diffuse retinal
degeneration leading to blindness by 4 months of age was seen in
affected kittens. All clinical signs were progressive and euthanasia
or death invariably occurred within the first few days to 7 months
of life, often due to upper respiratory disease or cardiac failure.
The clinical and radiographic features, lysosomal enzyme activities,
and mode of inheritance are homologous with ML II in humans. Feline
ML II is currently the only animal model in which to study the pathogenesis
of and therapeutic interventions for this unique storage disease.
Siamese
The mucopolysaccharidoses (MPS) are inherited metabolic disorders resulting from the defective catabolism of glycosaminoglycans.
Cowell KR, Jezyk PF,
Haskins ME, Patterson DF. 1976 Mucopolysaccharidosis in a cat. J
Am Vet Med Assoc. 169(3):334-9.
A young adult female Siamese cat born of a mother-son mating was referred because of dwarfism, facial abnormalities, severe skeletal deformities, multifocal neurologic deficits, and retinal atrophy. Cats of similar appearance had been observed in a previous litter of the same parents. Metachromatic inclusion bodies were demonstrated in circulating leukocytes. The urine contained a high concentration of mucopolysaccharide, as detected by the toluidine blue spot test. The uronic acid content of the cetylpyridinium chloride-precipitable mucopolysaccharide in the urine was 17 times greater than that in the urine from a control cat of the same age and breed.
Clinical signs: corneal clouding
Reference
Kakkis
ED, Schuchman E, He X, Wan Q, Kania S, Wiemelt S, Hasson CW, O'Malley
T, Weil MA, Aguirre GA, Brown DE, Haskins ME. 2001 Enzyme replacement
therapy in feline mucopolysaccharidosis I. Mol Genet Metab. 72(3):199-208.
ekakkis@biomarinpharm.com
Enzyme replacement therapy (ERT) has long been considered an approach to treating lysosomal storage disorders caused by deficiency of lysosomal enzymes. ERT is currently used to treat Gaucher disease and is being developed for several lysosomal storage disorders now that recombinant sources of the enzymes have become available. We have continued development of ERT for mucopolysaccharidosis I (MPS I) using the feline model. Recombinant alpha-L-iduronidase was administered intravenously at low dose (approximately 0.1 mg/kg or 25,000 units/kg) to four cats and high dose (0.5 mg/kg or 125,000 units/kg) to two cats on a weekly basis for 3- or 6-month terms. Clinical examinations showed distinct clearing of corneal clouding in one cat although clinical effects in the others were not evident. Biochemical studies of the cats showed that the enzyme was distributed to a variety of tissues although the liver and spleen contained the highest enzyme activities. Glycosaminoglycan storage was decreased in liver and spleen, and the histologic appearance improved in liver, spleen, and renal cortex. Enzyme was not consistently detected in cerebral cortex, brainstem, or cerebellum and the histologic appearance and ganglioside profiles did not improve. A variety of other tissues showed low variable uptake of enzyme and no distinct improvement. IgG antibodies to alpha-L-iduronidase were observed in five cats with higher titers noted when higher doses were administered. Mild complement activation occurred in three cats. Enzyme replacement therapy was effective in reversing storage in some tissues at the biochemical and histologic level in MPS I cats but an improved tissue distribution and prevention of a significant immune response could make the therapy more effective.
Siamese
Clinical signs: dwarfism, degenerative joint disease, skeletal deformities, facial dysmorphia due to epiphyseal dysplasia,degenerative joint disease, corneal clouding, and abnormal leukocyte inclusions.
References and abstracts.
Crawley
AC, Muntz FH, Haskins ME, Jones BR, Hopwood JJ. 2003 Prevalence
of mucopolysaccharidosis type VI mutations in Siamese cats.J Vet
Intern Med. 17(4):495-8.
allison.crawley@adelaide.edu.au
Mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease, is one of the more prevalent inherited diseases in cats and is commonly found in cats with Siamese ancestry. The prevalence of 2 known MPS VI mutations in cats was investigated in 101 clinically normal Siamese cats, in 2 cats with clinical signs of MPS VI, and in 202 cats from 4 research colonies. The mutation L476P which causes a severe clinical phenotype, was present on both alleles in the known MPS VI cats from Italy and North America and was present in all research colonies that originated from North America. However, LA76P was not detected in the Siamese population screened. In contrast, the mutation D520N, which causes a mild clinical phenotype, was identified in 23 of 202 (11.4%) alleles tested in Siamese cats from 3 continents, 2 of which were homozygous for D520N. Thus, the D520N mutation was widespread, and it is likely that cats inheriting both mutations (LA76P/D520N compound heterozygotes) would be in the general Siamese population, particularly in North America. Practitioners should note the high incidence of degenerative joint disease in these animals.
Crawley AC, Yogalingam G, Muller VJ, Hopwood
JJ. 1998 Two mutations within a feline mucopolysaccharidosis type
VI colony cause three different clinical phenotypes. J Clin Invest.
101(1):109-19
Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-4-sulfatase (4S). A feline MPS VI model used to demonstrate efficacy of enzyme replacement therapy is due to the homozygous presence of an L476P mutation in 4-sulfatase. An additional mutation, D520N, inherited independently from L476P and recently identified in the same family of cats, has resulted in three clinical phenotypes. L476P homozygotes exhibit dwarfism and facial dysmorphia due to epiphyseal dysplasia, abnormally low leukocyte 4S/betahexosaminidase ratios, dermatan sulfaturia, lysosomal inclusions in most tissues including chondrocytes, corneal clouding, degenerative joint disease, and abnormal leukocyte inclusions. Similarly, D520N/D520N and L476P/D520N cats have abnormally low leukocyte 4S/betahexosaminidase ratios, mild dermatan sulfaturia, lysosomal inclusions in some chondrocytes, and abnormal leukocyte inclusions. However, both have normal growth and appearance. In addition, L476P/D520N cats have a high incidence of degenerative joint disease. We conclude that L476P/D520N cats have a very mild MPS VI phenotype not previously described in MPS VI humans. The study of L476P/D520N and D520N/ D520N genotypes will improve understanding of genotype to phenotype correlations and the pathogenesis of skeletal dysplasia and joint disease in MPS VI, and will assist in development of therapies to prevent lysosomal storage in chondrocytes.
Ho TT, Maguire AM, Aguirre GD, Surace EM, Anand V, Zeng Y, Salvetti A, Hopwood JJ, Haskins ME, Bennett J. 2002 Phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI. J Gene Med. 4(6):613-21.
BACKGROUND: Mucopolysaccharidosis VI (MPS VI), due to recessively inherited 4-sulfatase (4S) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. Retinal involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine whether recombinant adeno-associated virus (AAV)-mediated delivery of 4S would reverse the RPE pathology seen in MPS VI cats. METHODS: AAV.f4S, containing the feline 4S cDNA, was delivered unilaterally to eyes of affected cats by subretinal or intravitreal injection. Contralateral eyes received AAV with the green fluorescent protein (GFP) reporter gene as control. At 2-11 months post-injection, the cats were sacrificed and the treatment effects were evaluated histologically. RESULTS: By ophthalmoscopy and histological analyses, GFP was evident as early as 4 weeks and persisted through the latest time point (11 months). Untreated and AAV.GFP-treated diseased retinas contained massively hypertrophied RPE cells secondary to accumulation of dilated lysosomal inclusions containing dermatan sulfate. MPS VI eyes treated subretinally with AAV.f4S had minimal RPE cell inclusions and, consequently, were not hypertrophied. CONCLUSIONS: AAV-mediated subretinal delivery of f4S provided correction of the disease phenotype in RPE cells of feline MPS VI, supporting the utility of AAV as a vector for the treatment of RPE-specific as well as lysosomal storage diseases.
Macri B, Marino F, Mazzullo G, Trusso A,
De Maria R, Amedeo S, Divari S, Castagnaro M. 2002 Mucopolysaccharidosis
VI in a Siamese/short-haired European cat. J Vet Med A Physiol Pathol
Clin Med. Oct;49(8):438-42.
A 3-year-old Siamese/short-haired European cat was referred for clinical disease characterized by dwarfism, facial dysmorphia, paralysis, small and curled ears, corneal clouding and large areas of alopecia. X-ray examination showed multiple bone dysplasia. On the basis of clinical features a form of mucopolysaccharidosis was suspected. The cat, killed at the owner's request, presented several severe skeletal deformities such as long caudal limbs, enlarged thorax with sunken breastbone, vertebral ankylosis in many spinal segments and visceral involvement. Histologically, the cat showed diffuse vacuolization and enlargement of cells in cartilage, bone and visceral organs. Ultrastructurally, membrane-bound vacuoles were filled with fibrillar and fluffy-material or concentrically whorled lamellae. Arylsulphatase B activity was 3.24 nm/mg/h in the affected cat and 30.6 in a normal age-matched control (NC). The L-iduronidase activity was slightly increas