Niemann-Pick disease type A

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).