Contributor: Gordon K. Klintworth
Niemann-Pick disease type I (sphingomyelinase deficiency, sphingomyelin phosphodiesterase 1 deficiency, OMIM #257200) is characterized by an onset from early infancy and a marked visceromegaly with nervous system involvement. Neurological deterioration is rapid and death occurs < 5 years of age. These cases of  Niemann-Pick disease have a primary sphingomyelin storage due to a deficiency of  sphingomyelinase and the activity of this enzyme is < 5% of normal.
This type of Niemann-Pick disease closely resembles three types of Niemann-Pick disease in the Crocker classification (Niemann-Pick disease type A, Niemann-Pick disease type B and Niemann-Pick disease type E) and it results from a mutation in the SMPD1 gene. An arginine-to-leucine substitution at amino acid residue 496 is present in many affected individuals, especially patients of Ashkenazi Jewish descent.
Niemann-Pick disease type I is ~10 times more frequent among individuals of Ashkenazi Jewish ancestry than in the general population. Niemann-Pick disease type I is subdivided into acute (Niemann-Pick disease type IA), subacute (Niemann-Pick disease type IB) and chronic (Niemann-Pick disease type IC) forms. Diagnosis of Niemann-Pick disease type I can be made by measuring the activity of sphingomyelinase in cultured skin fibroblasts, leukocytes, or biopsied pieces of tissue.