Niemann-Pick disease type C1 in domestic shorthaired cats

Niemann-Pick type C1disease is a lysosomal storage disease characterized by impaired transport and metabolism of un-esterified cholesterol and sphingomyelin. The accumulation of these substances in lysosomes and endosomes causes progressive neurological dysfunction. Clinical manifestations, such as head or whole-body tremor and poor coordination of movements (dysmetria, ataxia), are evident from about 8 to 12 weeks of age. Other signs include low birth weight, hepatosplenomegaly (i.e. enlargement of the liver and spleen) and premature death, typically around 8 to 10 months of age.

The disease can be caused by two different mutations in the NPC1 gene, which encodes the intracellular cholesterol transporter. These are the missense mutations c.2864G>C or c.1322A>C.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected kittens.

.

References:

Somers, KL., Royals, MA., Carstea, ED., Rafi, MA., Wenger, DA., Thrall, MA. : Mutation analysis of feline Niemann-Pick C1 disease. Mol Genet Metab 79:99-103, 2003. Pubmed reference: 12809639.

Mauler, D.A., Gandolfi, B., Reinero, C.R., O'Brien, D.P., Spooner, J.L., Lyons, L.A. : Precision medicine in cats: Novel Niemann-Pick type C1 diagnosed by whole-genome sequencing. J Vet Intern Med 31:539-544, 2017. Pubmed reference: 28233346.