Felis ISSN 2398-2950

Feline autoimmune lymphoproliferative syndrome (FALPS)

Synonym(s): ALPS

Contributor(s): John Munday, Danielle Aberdein

Introduction

  • Feline autoimmmune lymphoproliferative syndrome (FALPS) is an inherited condition seen in British shorthair (BSH) and BSH-cross breeds.
  • Cause: genetic, due to inherited mutations in the Fas ligand gene. Kittens homozygous for the mutation develop FALPS, while heterozygotes are clinically unaffected but carry the mutation and may pass it to offspring. The feline disease is analogous to the inherited disease autoimmune lymphoproliferative syndrome (ALPS) in people.
  • Signs: affected kittens appear normal at birth but show failure to thrive, lethargy, regenerative anemia, abdominal distension and marked generalized lymphadenopathy from 6-12 weeks of age.  
  • Diagnosis: genetic testing, lymph node cytology, histology, immunohistochemistry, and PCR for antigen receptor rearrangements (PARR) testing.
  • Treatment: none known.
  • Prognosis: grave. To date, all reported cases of FALPS have been fatal or have required euthanasia on humane grounds between 2-4 months of age. 

Pathogenesis

Etiology

  • Monogenic autosomal recessive mutation in the Fas-ligand gene.
  • Kittens homozygous for the mutation develop FALPS at a young age.
  • Kittens heterozygous for the mutation are carriers of the disease but are clinically normal and do not develop FALPS.

Pathophysiology

  • The Fas ligand gene codes for proteins critical in normal cell apoptosis.
  • The mutation causing FALPS involves the insertion of an adenine base in exon 3 of the Fas ligand gene.
  • This causes a frameshift mutation and insertion of a premature stop codon, predicted to produce a truncated Fas ligand protein that is unlikely to initiate effective lymphocyte apoptosis. Consequent lymphocyte proliferation results. 

Diagnosis

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Treatment

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Prevention

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Aberdein D, Munday J S, Dittmer K E, Heathcott R W, Lyons L A (2017) Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand. NZ Vet J 65, 327-331 PubMed.
  • Aberdein D, Munday J S, Gandolfi B, Dittmer K E, Malik R, Garrick D J, Lyons L A; 99 Lives Consortium. (2016) A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats. Mamm Genome 28, 47-55 PubMed.
  • Aberdein D, Munday J S, Fairley R A, Vernau W, Thompson K G (2015) A novel and likely inherited lymphoproliferative disease in British shorthair kittens. Vet Pathol 52, 1176-1182 PubMed.

Organisation(s)


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