Handbook of Genetic Counseling/Niemann-Pick Disease-2
Niemann-Pick Disease
(Type A)
Background
[edit | edit source]- 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
[edit | edit source]- 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
[edit | edit source]- Within Ashkenazi Jewish population:
- Incidence: 1 in 40,000
- Carrier frequency: 1 in 90
Diagnosis
[edit | edit source]- 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 | edit source]- 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
[edit | edit source]- Autosomal recessive
Testing
[edit | edit source]- Ashkenazi Jewish panel is available clinically:
- Carrier and prenatal also available for known family mutations
Management & Treatment
[edit | edit source]- 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 | edit source]- Early death of child
- Loss of developmental milestones
Patient Resources
[edit | edit source]- 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
References
[edit | edit source]- Molecular Basis of Metabolic Disease
- Web:
- Genzyme: http://www.genzymegenetics.com/Our-Services/Reproductive-Testing/niemann-pick-disease-type-a-testing.aspx
- Baylor: http://www.bcmgeneticlabs.org/tests/dna/niemannpick.html
Notes
[edit | edit source]- The information in this outline was last updated in Feb 2003.