The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations

Am J Hum Genet. 2002 Dec;71(6):1413-9. doi: 10.1086/345074. Epub 2002 Oct 4.


We have collected demographic and/or mutation information on a worldwide sample of 394 patients with type B Niemann-Pick disease (NPD). The disorder is panethnic, with the highest incidence occurring in individuals of Turkish, Arabic, and North African descent. Only five of the 394 patients were Ashkenazi Jewish, revealing that, unlike the type A form of NPD, type B NPD does not occur frequently within this population. Mutation analysis of the acid sphingomyelinase (ASM) gene (designated "SMPD1") was performed on 228 patients (324 unique alleles), and several novel, "common" mutations were found. Among these were the L137P, fsP189, and L549P mutations, which accounted for approximately 75% of the alleles in Turkish patients, the H421Y and K576N mutations, which accounted for approximately 85% of the alleles in Saudi Arabian patients, the S379P, R441X, R474W, and F480L mutations, which accounted for approximately 55% of the alleles in Portuguese/Brazilian patients, and the A196P mutation, which accounted for approximately 42% of the alleles in Scottish/English patients. The previously reported DeltaR608 mutation occurred on approximately 12% of the alleles studied. Overall, a total of 45 novel mutations were found, and several new genotype/phenotype correlations were identified. In particular, the L137P, A196P, and R474W mutations were consistent with a less severe form of type B NPD, whereas the H421Y and K576N mutations led to an early-onset, more severe form that was specific to Saudi Arabia. These data provide the first extensive demographic assessment of this disorder and describe several new mutations that can be used to predict phenotypic outcome and to gain new insights into the structure and function of ASM.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Binding Sites
  • DNA Mutational Analysis
  • Demography
  • Ethnicity / genetics*
  • Gene Frequency
  • Genotype
  • Humans
  • Incidence
  • Mutation / genetics*
  • Niemann-Pick Diseases / classification
  • Niemann-Pick Diseases / epidemiology*
  • Niemann-Pick Diseases / genetics*
  • Phenotype
  • Protein Structure, Tertiary
  • Sphingomyelin Phosphodiesterase / chemistry
  • Sphingomyelin Phosphodiesterase / genetics*
  • Sphingomyelin Phosphodiesterase / metabolism
  • Structure-Activity Relationship


  • acid sphingomyelinase-1
  • Sphingomyelin Phosphodiesterase

Associated data

  • OMIM/257200