Niemann-Pick disease, Type A

Gene: SMPD1

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, (nonsense), SMPD1 gene; c.1017 G>A, p.(W339 STOP), exon2, chromosome D1.

Breeds: Balinese, Domestic Cat, Siamese

Medical system: (Lysosomal storage disease); neurological, respiratory, hepatic, renal, immune systems.

Age of onset of symptoms: By about 4 months of age.

Niemann-Pick disease type A (NPD type A) is an autosomal recessive genetic disease described in several animal species including humans and cats.  It is a lysosomal storage disease, caused by an enzyme defect resulting in an accumulation of the lipids sphingomyelin and cholesterol within cells.  NPD type A presents as a rapidly progressing demyelinating polyneuropathy with gait disorders and intention tremors, and results in an early death.  In cats, NPD type A has historically been observed sporadically in Siamese and Balinese breeds and within the domestic cat populations.  Although the pathology of the disease has been studied in these animals, the causal mutations were not characterized.  More recently, NPD type was diagnosed in a domestic kitten and molecular characterization revealed an inactivating mutation within the SMPD1 gene.  SMPD1 codes for the acid sphingomyelinase enzyme which normally digests sphingomyelin and prevents its cellular accumulation.  Because of its sporadic incidence with mortality occurring before reproductive maturity, NPD type A in cats is of more academic interest to scientists than it is of clinical concern to veterinarians or of practical concern to cat breeders.

Niemann-Pick disease in the cat can be caused by mutations in additional genes:

Niemann-Pick disease, type C1(NPC1 gene). OMIA link [0725-9685]

Niemann-Pick disease, type C2 (NPC2 gene). OMIA link [2065-9685]

References:

OMIA link: [1795-9685]

Takaichi Y, Chambers JK, Kok MK, et al. (2020) Feline Niemann-Pick disease with a novel mutation of SMPD1 gene. Vet Pathol 57:559-564.  [pm/32347185]

Cuddon PA, Higgins RJ, Duncan ID. et al. (1989) Polyneuropathy in feline Niemann-Pick disease. Brain 112 (Pt 6):1429-43.  [pm/2557121]

Wenger DA, Sattler M, Kudoh T, et al. (1980) Niemann-Pick disease: a genetic model in Siamese cats Science 208:1471-3. [pm/7189903]

Contributed by: Justine Bilodeau and Agathe Frainais, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)