ISSN 2398-2969      

Niemann Pick disease


Mark Lowrie

Nicolas Granger

Synonym(s): Sphingomyelinosis, Storage disease


  • Niemann Pick Disease (sphingomyelinosis) is a condition belonging to a group of genetic disorders known as storage diseases. 
  • They are classified as Niemann Pick Disease Types A to C in people. 
  • Only Type A and C (the latter designated as C1 and C2) are described in veterinary patients with a phenotypic variant of type A described in Siamese cats. 
  • Dogs not commonly affected. 
  • Lysosomal storage disorders (LSDs) are a heterogeneous group of genetic diseases characterized by defective function in one of the lysosomal enzymes. 
  • Failure of the metabolic pathway → accumulation of incompletely degraded macromolecules → impaired cellular function. 
  • Multifocal neurological signs. 
  • Cause: specific enzyme deficiency due to genetic anomaly/mutation, may occur as breed-specific inherited disease. Usually autosomal recessive mode of inheritance. 
  • Signs: chronic, progressive neurological signs - ataxia, hypermetria, intentional tremors, loss of balance, paresis, and forebrain signs. 
  • Diagnosis: lysosomal enzyme analysis or molecular genetic testing. 
  • Treatment: none. Possible gene therapies emerging from pre-clinical studies.
  • Prognosis: poor.



  • Sphingomyelinosis - deficiency of sphingomyelinase:
    • No mutations identified in dogs. Cat mutations listed below: 
      • Type A has been associated with a mutation in the SMPD1 gene affecting a 4 month old mixed breed cat (sphingomyelin phosphodiesterase 1). 
      • Type C1 has been associated with two mutations in the NPC1 gene. 
      • Type C2 has been associated with a mutation in the NPC2 gene.

Predisposing factors


  • Most of these breed-specific diseases are thought to be hereditary (usually as an autosomal recessive inheritance). 


  • Pathophysiology assumed to be similar to cats. See below: 
    • Type A - defect in gene coding for SMPD1 gene that codes for the sphingomyelinase gene → accumulation of sphingomyelin. 
    • Type C (1 and 2) - defect in genes NPC1 and NPC2 which code for proteins in the membranes of lysosomes and endosomes involved in lipid movement. 
    • Lipids and proteins are usually broken down into smaller components to provide energy for the body. In Niemann-Pick disease, harmful quantities of lipids accumulate in the brain, spleen, liver, lungs, and bone marrow.  


  • Quickly progressive over months. 


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Further Reading


Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Pallottini V, Pfrieger  FW (2020) Understanding and treating Niemann-Pick type C disease: Models matter. Int J Mol Sci 21, E8979 PubMed
  • Switonski M (2020) Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies. J Appl Genet 61(2),179-186 PubMed.
  • Takaichi Y, Chambers J K, Kok M K, Uchiyama H, Haritani M, Hasegawa D, Nakayama H, Uchida K (2020) Feline Niemann-Pick Disease With a Novel Mutation of  SMPD1 Gene. Vet Pathol 300985820921810 PubMed DOI: 10.1177/0300985820921810.
  • Mauler D A, Gandolfi B, Reinero C R, O'Brien D P, Spooner J L, Lyons L A (2017) Precision Medicine in Cats: Novel Niemann-Pick Type C1 Diagnosed by Whole-Genome Sequencing. JVIM 31, 539-544 PubMed
  • 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 (2016) Cerebrospinal Fluid Calbindin D Concentration as a Biomarker of Cerebellar Disease Progression in Niemann-Pick Type C1 Disease. J Pharmacol Exp Ther 358, 254-261 PubMed
  • Bradbury A M, Gurda B L, Casal M L, Ponder K P, Vite C H, Haskins M E (2015) A review of gene therapy in canine and feline models of lysosomal storage disorders. Hum Gene Ther Clin Dev 26(1), 27-37 PubMed.
  • 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 (2015) Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease. Sci Transl Med 7, 276ra26 PubMed
  • Zampieri S, Bianchi E, Cantile C, Saleri R, Bembi B, Dardis A (2014) Characterization of a spontaneous novel mutation in the NPC2 gene in a cat affected by Niemann Pick type C disease. PLoS One 9, e112503 PubMed
  • Bagel J H, Sikora T U, Prociuk M, Pesayco J P, Mizisin A P, Shelton G D, Vite C H (2013) 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, 256-262 PubMed
  • Roszell B R, Tao J Q, Yu K J, Gao L, Huang S, Ning Y, Feinstein S I, Vite C H, Bates S R (2013) Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease. PLoS One 8, e67084 PubMed
  • 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 (2012) Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C. J Neuropathol Exp Neurol 71, 434-448 PubMed
  • Ward S, O'Donnell P, Fernandez S, Vite C H (2010) 2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease. Pediatr Res 68, 52-56 PubMed.  
  • Vite C H, Ding W, Bryan C, O'Donnell P, Cullen K, Aleman D, Haskins M E, Van Winkle T (2008) Clinical, electrophysiological, and serum biochemical measures of progressive neurological and hepatic dysfunction in feline Niemann-Pick type C disease. Pediatr Res 64, 544-549 PubMed.  
  • Somers K L, Royals M A, Carstea E D, Rafi M A, Wenger D A, Thrall M A (2003) Mutation analysis of feline Niemann-Pick C1 disease. Mol Genet Metab 79, 99-103 PubMed.
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  • Somers K L, Brown D E, Fulton R, Schultheiss P C, Hamar D, Smith M O, Allison R, Connally H E, Just C, Mitchell TW, Wenger D A, Thrall M A (2001) Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease. J Inherit Metabol Dis 24, 427-436 PubMed.  
  • Somers K L, Wenger D A, Royals M A, Carstea E D, Connally H E, Kelly T, Kimball R, Thrall M A (1999) Complementation studies in human and feline Niemann-Pick type C disease. Mol Genet Metab 66, 117-21 PubMed.   
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