Handbook of Genetic Counseling/Niemann-Pick Disease-2

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Niemann-Pick Disease

(Type A)


  • Niemann-Pick disease is a neurodegenerative disease caused by a lysosomal storage disorder. A deficiency in acid sphingomyelinase (ASM) activity results in the accumulation of sphingomyelin.


  • Caused by mutation in ASM gene
  • Chromosomal location 11p15.1-p15.4
  • 18 causal mutations mapped
  • 3 mutations account for 92% of Ashkenazi Jewish (R496L, L302P, and fsP330)


  • Within Ashkenazi Jewish population:
  • Incidence: 1 in 40,000
  • Carrier frequency: 1 in 90


  • Clinical-
  • Hepatosplenomegaly
  • Developmental delay and loss of milestones
  • Presence of "Niemann-Pick" foam cells in bone marrow aspirates
  • Enzymatic-
  • ASM activity below 5% or normal
  • Molecular-
  • Mutation found in ASM gene

Natural History[edit]

  • Perinatal:
  • Generally unremarkable:
  • Prolonged jaundice in neonatal period occasionally
  • Early infancy:
  • Around 3 Months:
  • Hepatosplenomegaly noted by physical exam
  • "Niemann-pick" foam cells present in bone marrow aspirates
  • Moderate anemia may be present
  • Hypotonia and muscular weakness, feeding difficulties
  • By 6 months:
  • Psychomotor retardation evident
  • Loss of developmental milestones
  • Cherry-red maculae noted in ophthalmologic exam (50%)
  • Loss of deep tendon reflexes
  • Progression:
  • Continued loss of motor function
  • Deterioration of intellectual capabilities
  • Emaciation, spasticity, and rigidity
  • Death occurs by 2-3 years of age


  • Autosomal recessive


  • Ashkenazi Jewish panel is available clinically:
  • Carrier and prenatal also available for known family mutations

Management & Treatment[edit]

  • There is currently no treatment for Niemann-Pick disease
  • Differential Diagnosis
  • Niemann-Pick disease Type C and D
  • Gaucher Disease
  • Other storage disorders

Psychosocial Issues[edit]

  • Early death of child
  • Loss of developmental milestones

Patient Resources[edit]

  • National Niemann-Pick Disease Foundation
PO Box 49
415 Madison Ave
Ft. Atkinson, WI 53538
Email: nnpdf @idcnet.com



  • The information in this outline was last updated in Feb 2003.