Home > D. Systemic pathology > Genetic and developmental anomalies > Genetic metabolic diseases > Niemann-Pick disease type A

Niemann-Pick disease type A

Monday 3 April 2006

Synopsis

- autosomal recessive disease
- short stature
- low body weight
- failure to thrive
- cherry-red maculae (50%)
- gray, granular-appearing maculae
- frequent respiratory infections
- diffuse reticular or finely nodular infiltrations
- protuberant abdomen
- hepatomegaly
- neonatal jaundice
-  splenomegaly
- vomiting
- constipation
- feeding difficulties
- osteoporosis
- xanthomas
- hypotonia
- muscle weakness
- hyporeflexia
- psychomotor retardation
- mental retardation
- spasticity (later)
- rigidity (later)
- athetosis (later)
- microcytic anemia

PAthology

- large vacuolated foam cells (’NP cells’) on bone marrow biopsy
- sea blue histiocytes
- lymphadenopathy
- multiple organs (lung, liver, spleen, kidney, brain) contain foamy resident cells and histiocytes
- Electron microscopy: foam cells shows lamellar inclusions

LABORATORY ABNORMALITIES

- Decreased acid sphingomyelinase activity (less than 5%)

MISCELLANEOUS :
- onset in infancy
- death by age 3 years
- more common in Ashkenazi Jews
- allelic disorder to Nieman-Pick disease type B (NPC) (MIM.607616)

Etiology

-  Niemann-Pick disease type A is caused by mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1) (MIM.607608), which encodes acid sphingomyelinase (ASM).