Handbook of Genetic Counseling/Niemann-Pick Disease-2

Niemann-Pick Disease

(Type A)

Background

 * 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.

Genetics

 * 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)

Incidence

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

Diagnosis

 * 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

 * 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

Inheritance

 * Autosomal recessive

Testing

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

Management & Treatment

 * 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

 * Early death of child
 * Loss of developmental milestones

Patient Resources

 * National Niemann-Pick Disease Foundation
 * PO Box 49
 * 415 Madison Ave
 * Ft. Atkinson, WI 53538
 * (877)-287-3672
 * (920)-563-0930
 * Email: nnpdf @idcnet.com