What's in a name? Using signalment to guide your diagnoses (Proceedings)


What's in a name? Using signalment to guide your diagnoses (Proceedings)

Aug 01, 2011

Knowledge of breed predispositions and inherited disorders can direct your differential diagnoses and your diagnostic plan. For some of these diseases the genetic mutation has been identified and tests for the defect have been developed. For others, the phenotypical characteristics have been well-described but the genetic basis and mode of inheritance are unknown. This lecture is not a presentation on genetics, but rather a general discussion of several feline breeds that have recognized diseases, both common and unusual, that veterinarians should consider when presented with these patients.

Chediak-Higashi Syndrome [Persians]

This autosomal recessive disease affects both neutrophils and platelets in a variety of ways. Unlike in humans, neutropenia is not always present in cats, but the neutrophils are filled with large granules that may impair the destruction of microorganisms. Platelets are also affected, lacking granules that contain platelet agonists important for clotting. The clinical consequences of these two defects are immunodeficiency, especially recurrent bacterial infections, and prolonged bleeding times. In addition, cats may have a variety of ocular abnormalities, including light sensitivity, red-gray retinas, reduced tapetal reflection, early cataracts, and spontaneous nystagmus. Because large melanin granules form in the skin, they often have a "blue smoke" fur color. There is no treatment for the disorder, but care must be taken to manage bleeding during procedures.

Systemic amyloidosis (liver) [Siamese and Oriental breeds] (kidney) [Abyssinian]

In Siamese cats, the sequence of the Amyloid A protein is distinct from that of Abyssinians which may account for its predilection for hepatic deposition in systemic amyloidosis in Siamese and other related breeds. Cats are generally young, ranging from 10 months to 7 years [mean: 3.5 yrs]. In one study, females predominated, but males were more prevalent in another. Diagnosis is often made after acute intra-abdominal hemorrhage from ruptured hepatic parenchyma. Cats in one case series had intermittent episodes accompanied by collapse, anemia, and anorexia. Hepatomegaly may be palpable; ALT is usually elevated to a greater extent than would be expected from hypoxia secondary to anemia. On ultrasound, hepatic parenchyma had a diffuse, "heterogeneous echogenicity with highly echogenic ('sparkling') areas and hypoechoic foci." Fine needle aspirate of the liver may reveal evidence of amyloid deposition. A large, friable liver, often with subcapsular hemorrhage, is found on abdominal exploratory. Therapy with colchicine has been attempted, but prognosis is poor. Some evidence suggests that vitamin K therapy should be instituted to normalize bleeding disorders, since clotting abnormalities can be seen in human amyloidosis, but this has not been substantiated in cats. Systemic amyloidosis of Abyssinians affects the kidney and results in fatal renal disease. It is an autosomal dominant trait with incomplete penetrance. The deposition occurs in the medulla in all affected cats and in the glomeruli in 75% of cats and results in papillary necrosis and interstitial nephritis/fibrosis. Cats present between the ages of 1 to 5 years of age with chronic renal failure, but amyloid deposition first occurs between 9 – 24 months of age. However, some cats have minimal amyloid deposition and may not develop overt renal disease. Amyloid deposition can occur elsewhere but the major clinical consequence of systemic amyloidosis is chronic renal failure.

Pyruvate Kinase Deficiency [Abyssinians and Somalis]

Pyruvate kinase is essential for ATP production in the red blood cell. Without PK, important functions, such as maintenance of the RBC membrane and membrane transport, are not possible, resulting in decreased erythrocyte lifespan and hemolytic anemia. PK deficiency has been documented in Abyssinians and Somalis in the U.S., Europe and Australia with 23-31% of these breeds classified as carriers. Clinical signs are variable, depending upon the severity of the disease. In one study, the most commonly documented clinical features were lethargy, diarrhea, pale mucous membranes, inappetence, poor haircoat and weight loss. Cats may be asymptomatic or exhibit clinical signs only during times of stress. A high reticulocyte count may be apparent on the CBC, evidence that the bone marrow is replacing short-lived erythrocytes. The onset of clinical disease is usually less than 3 years of age; lifespan is variable depending upon the severity of the anemia and the frequency of the hemolytic episodes. Treatment is symptomatic, i.e., blood transfusions as necessary. Limiting stress also appears to be important. Splenectomy has been used successfully in humans and other species, including cats, but is not the first line of therapy. Culling all cats that are PK-deficient is not wise, due to the concern of creating a genetic bottleneck. Judicious use of unaffected cats for breeding programs and breeding carriers with non-carriers will help reduce the disease prevalence over time.