Genetic basis of Autoimmune Lymphoproliferative Syndrome - in cats, also referred to as Feline Autoimmune Lymphoproliferative Syndrome (FALPS), is an autosomal recessive inherited disorder caused by a mutation in the FAS ligand gene (FASLG). Affected cats inherit two copies of the mutation (one from each parent). Heterozygous carriers have one copy of the defective gene and remain clinically normal but can pass on the mutation. This mutation leads to a truncated, non-functional Fas ligand protein that impairs normal apoptosis (programmed cell death) of lymphocytes, resulting in uncontrolled lymphocyte proliferation. The disease has so far been reported primarily in British Shorthair (BSH) cats in New Zealand and Australia, associated with a specific insertion mutation in exon 3 of FASLG (c.418insA). Genetic testing is available through specialized veterinary genetic labs to identify affected, carrier, and clear cats.
Pathophysiology - The Fas ligand protein is essential for inducing apoptosis in immune cells, including lymphocytes. The FASLG mutation leads to failure of Fas-mediated apoptosis, causing accumulation and proliferation of lymphocytes (lymphoproliferation). This disrupts immune homeostasis and leads to clinical signs such as generalized lymphadenopathy and splenomegaly. The defective apoptosis also causes autoimmune features, including hemolytic anemia.
Complications - Clinical manifestations typically appear by 6 weeks of age, including: Generalized lymphadenopathy (enlarged lymph nodes). Moderate splenomegaly (enlarged spleen). Regenerative hemolytic anemia. Lethargy, weight loss, abdominal distension. Severe immune dysregulation leading to fatal outcomes within a few months if untreated. No currently known effective treatments; disease progression is severe and usually fatal, often requiring humane euthanasia between 2–4 months of age.
Why This Matters to Breeders and Vets - Breeders must use genetic testing to identify carriers of the FASLG mutation to avoid breeding two carriers, which results in a 25% chance of producing affected kittens. Preventing carrier matings is key to controlling this fatal disease within the breed.
Veterinarians should recognize early signs in young British Shorthair kittens and confirm diagnosis with genetic testing and clinical pathology. Differentiating ALPS from other causes of lymphadenopathy and anemia is essential. Early genetic diagnosis allows for informed breeding advice and reduces disease incidence. Currently, there are no effective treatments, making genetic prevention vital.
Summary - Autoimmune Lymphoproliferative Syndrome (ALPS) in cats is a rare autosomal recessive immune disorder caused by mutations in the FAS ligand gene, leading to defective lymphocyte apoptosis and lymphoproliferation. It presents mainly in British Shorthair cats as early-onset generalized lymphadenopathy, splenomegaly, and hemolytic anemia, culminating in a fatal outcome in young kittens. Genetic testing is essential for identifying carriers and affected animals, allowing breeders and veterinarians to manage and reduce this severe hereditary disease. No curative treatments are currently available.