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