OMIA:000725-9685 : Niemann-Pick disease, type C1 in Felis catus (domestic cat)

In other species: dog , taurine cattle

Categories: Lysosomal storage disease , Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 257220 (trait) , 607623 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2003

Cross-species summary: Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disease (LSD) characterised by impaired un-esterified cholesterol and sphingomyelin transport and metabolism, resulting in the accumulation of un-esterified cholesterol and glycosphingolipids within late endosomes and lysosomes. Affected animals present with hepatosplenomegaly, neurological degeneration and premature death.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Somers et al. (2003) showed that this disorder is due to a 2864G>C base substitution in the NPC1 gene, resulting in a C955S amino-acid substitution. In an excellent example of Precision Medicine (and the first time this term has appeared in the 24,392 papers currently [29 Oct 2016] included in OMIA), Mauler et al. (2017) identified a novel likely causal (missense) variant (c.1322A>C; p.H441P) in the NPC1 gene by 25x whole-genome sequencing an affected cat and comparing its variants to those in the 99 Lives Cat Genome Sequencing database.

Clinical features: NPC1 disease is a fatal neurovisceral lysosomal storage disease characterised by progressive neurological dysfunction. From around 8 to 12 weeks of age, head and whole-body intention tremors are observable and neurologic symptoms rapidly progress to severe dysmetria and ataxia (Munana et al., 1994). Other clinical features include low birth weight, hepatosplenomegaly and premature death, typically around 8 to 10 months of age (Brown et al., 1994; Vite et al., 2008). Serum biochemical abnormalities (elevations in liver enzymes, cholesterol, bile acids and total bilirubin and decreased albumin) are suggestive of hepatic disease but signs of jaundice and liver failure have not been observed in affected cats (Brown et al., 1994; Vite et al., 2008). IT thanks DVM student Daisy Lau, who provided the basis of this contribution in May 2023.

Pathology: Neuropathological features include diffuse neuronal cytoplasmic vacuolisation with intracellular cholesterol accumulation, severe Purkinje cell loss, GABAergic neuroaxonal dystrophy, ectopic dendritogenesis and central myelin deficits (Munana et al., 1994; Vite et al., 2008). Examination of liver histologic samples revealed extensively severe cytoplasmic vacuolisation of hepatocytes and Kupffer cells accompanied by marked accumulation of unesterified cholesterol (Vite et al., 2008). Multifocal histiocytosis with vacuolated macrophages were present in spleen and lung samples (Vite et al., 2008; Roszell et al., 2013). IT thanks DVM student Daisy Lau, who provided the basis of this contribution in May 2023.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NPC1 Niemann-Pick disease, type C1 Felis catus D3 NC_058379.1 (46107852..46053183) NPC1 Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
134 Domestic Shorthair Niemann-Pick disease, type C1 NPC1 missense Naturally occurring variant Felis_catus_9.0 D3 g.48234217C>G c.2864G>C p.(C955S) rs5334475149 2003 12809639 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
146 Domestic Shorthair Niemann-Pick disease, type C1 NPC1 missense Naturally occurring variant Felis_catus_9.0 D3 g.48250290T>G c.1322A>C p.(H441P) rs5334475146 2017 28233346 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000725-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2020 Pallottini, V., Pfrieger, F.W. :
Understanding and treating Niemann-Pick type C disease: Models matter. Int J Mol Sci 21:E8979, 2020. Pubmed reference: 33256121. DOI: 10.3390/ijms21238979.
2018 Gurda, B.L., Bagel, J.H., Fisher, S.J., Schultz, M.L., Lieberman, A.P., Hand, P., Vite, C.H., Swain, G.P. :
LC3 Immunostaining in the Inferior Olivary Nuclei of Cats With Niemann-Pick Disease Type C1 Is Associated With Patterned Purkinje Cell Loss. J Neuropathol Exp Neurol 77:229-245, 2018. Pubmed reference: 29346563. DOI: 10.1093/jnen/nlx119.
2017 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. DOI: 10.1111/jvim.14599.
2016 Bradbury, A., Bagel, J., Sampson, M., Farhat, N., Ding, W., Swain, G., Prociuk, M., O'Donnell, P., Drobatz, K., Gurda, B., Wassif, C., Remaley, A., Porter, F., Vite, C. :
Cerebrospinal fluid calbindin D concentration as a biomarker of cerebellar disease progression in Niemann-Pick type C1 disease. J Pharmacol Exp Ther 358:254-61, 2016. Pubmed reference: 27307499. DOI: 10.1124/jpet.116.232975.
2015 Vite, C.H., Bagel, J.H., Swain, G.P., Prociuk, M., Sikora, T.U., Stein, V.M., O'Donnell, P., Ruane, T., Ward, S., Crooks, A., Li, S., Mauldin, E., Stellar, S., De Meulder, M., Kao, M.L., Ory, D.S., Davidson, C., Vanier, M.T., Walkley, S.U. :
Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease. Sci Transl Med 7:276ra26, 2015. Pubmed reference: 25717099. DOI: 10.1126/scitranslmed.3010101.
2013 Bagel, J.H., Sikora, T.U., Prociuk, M., Pesayco, J.P., Mizisin, A.P., Shelton, G.D., Vite, C.H. :
Electrodiagnostic testing and histopathologic changes confirm peripheral nervous system myelin abnormalities in the feline model of niemann-pick disease type C. J Neuropathol Exp Neurol 72:256-62, 2013. Pubmed reference: 23399903. DOI: 10.1097/NEN.0b013e318286587f.
Roszell, B.R., Tao, J.Q., Yu, K.J., Gao, L., Huang, S., Ning, Y., Feinstein, S.I., Vite, C.H., Bates, S.R. :
Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease. PLoS One 8:e67084, 2013. Pubmed reference: 23843985. DOI: 10.1371/journal.pone.0067084.
2012 Stein, V.M., Crooks, A., Ding, W., Prociuk, M., O'Donnell, P., Bryan, C., Sikora, T., Dingemanse, J., Vanier, M.T., Walkley, S.U., Vite, C.H. :
Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C. J Neuropathol Exp Neurol 71:434-48, 2012. Pubmed reference: 22487861. DOI: 10.1097/NEN.0b013e31825414a6.
2010 Ward, S., O'Donnell, P., Fernandez, S., Vite, C.H. :
2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease. Pediatr Res 68:52-6, 2010. Pubmed reference: 20357695. DOI: 10.1203/PDR.0b013e3181df4623.
2008 Vite, CH., Ding, W., Bryan, C., O'Donnell, P., Cullen, K., Aleman, D., Haskins, ME., Van Winkle, T. :
Clinical, electrophysiological, and serum biochemical measures of progressive neurological and hepatic dysfunction in feline Niemann-Pick type C disease. Pediatr Res 64:544-9, 2008. Pubmed reference: 18614965. DOI: 10.1203/PDR.0b013e318184d2ce.
2003 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.
2002 Garver, W.S., Somers, K., Krishnan, K., Mitchell, T., Heidenreich, R.A., Thrall, M.A. :
The Niemann-Pick C1 protein in feline fibroblasts. Mol Genet Metab 76:31-6, 2002. Pubmed reference: 12175778. DOI: 10.1016/s1096-7192(02)00015-x.
2001 Somers, K.L., Brown, D.E., Fulton, R., Schultheiss, P.C., Hamar, D., Smith, M.O., Allison, R., Connally, H.E., Just, C., Mitchell, T.W., Wenger, D.A., Thrall, M.A. :
Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease Journal of Inherited Metabolic Disease 24:427-436, 2001. Pubmed reference: 11596647.
Zervas, M., Dobrenis, K., Walkley, S.U. :
Neurons in Niemann-Pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations. J Neuropathol Exp Neurol 60:49-64, 2001. Pubmed reference: 11202175. DOI: 10.1093/jnen/60.1.49.
1999 Somers, K.L., Wenger, D.A., Royals, M.A., Carstea, E.D., Connally, H.E., Kelly, T., Kimball, R., Thrall, M.A. :
Complementation studies in human and feline Niemann-Pick type C disease. Mol Genet Metab 66:117-21, 1999. Pubmed reference: 10068514. DOI: 10.1006/mgme.1998.2778.
1997 March, P.A., Thrall, M.A., Brown, D.E., Mitchell, T.W., Lowenthal, A.C., Walkley, S.U. :
Gabaergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C. Acta Neuropathol 94:164-72, 1997. Pubmed reference: 9255392. DOI: 10.1007/s004010050689.
1996 Brown, D.E., Thrall, M.A., Walkley, S.U., Wurzelmann, S., Wenger, D.A., Allison, R.W., Just, C.A. :
Metabolic abnormalities in feline Niemann-Pick type C heterozygotes Journal of Inherited Metabolic Disease 19:319-330, 1996. Pubmed reference: 8803775.
1994 Brown, D.E., Thrall, M.A., Walkley, S.U., Wenger, D.A., Mitchell, T.W., Smith, M.O., Royals, K.L., March, P.A., Allison, R.W. :
Feline Niemann-Pick disease type C American Journal of Pathology 144:1412-1415, 1994. Pubmed reference: 8203477.
Munana, K.R., Luttgen, P.J., Thrall, M.A., Mitchell, T.W., Wenger, D.A. :
Neurological manifestations of Niemann-Pick disease type-C in cats. J Vet Intern Med 8:117-21, 1994. Pubmed reference: 8046674. DOI: 10.1111/j.1939-1676.1994.tb03208.x.
1990 Lowenthal, A.C., Cummings, J.F., Wenger, D.A., Thrall, M.A., Wood, P.A., Delahunta, A. :
Feline sphingolipidosis resembling Niemann-Pick disease type-C. Acta Neuropathol 81:189-97, 1990. Pubmed reference: 2127982. DOI: 10.1007/BF00334507.
1989 Cuddon, P.A., Higgins, R.J., Duncan, I.D., Miller, S.P.F., Parent, J.M., Moser, A.B. :
Polyneuropathy in feline Niemann-Pick disease. Brain 112 ( Pt 6):1429-43, 1989. Pubmed reference: 2557121. DOI: 10.1093/brain/112.6.1429.
1971 Percy, D.H., Jortner, B.S. :
Feline lipidosis. Light and electron microscope studies Archives of Pathology 92:136-144, 1971.
1970 Crisp, C.E., Ringler, D.H., Abrams, G.D., Radin, N.S., Brenkert, A. :
Lipid storage disease in a Siamese cat J Am Vet Med Assoc 156:616-22, 1970. Pubmed reference: 5461697.

Edit History

  • Created by Frank Nicholas on 26 Nov 2007
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 21 Sep 2012
  • Changed by Frank Nicholas on 29 Oct 2016
  • Changed by Frank Nicholas on 20 May 2017
  • Changed by Imke Tammen2 on 04 Jun 2023