Loss of sphingomyelinase found in lysosomes, which are important to breakdown molecules leading to accumulation of sphingomyelin
- Sphingomyelinase deficiency
- Commoner in Ashkenazi jews.
- Ashkenazi Jewish population (NPA and NPB)
- French Canadian population of Nova Scotia (Type D, now considered a variant of Type C or NPC)
- Maghreb region (Tunisia, Morocco, and Algeria) of North Africa (NPB)
- Spanish-American population of southern New Mexico and Colorado (NPC)
- Type A, type B: mutations in the SMPD1 gene.
- Type C1, and type C2: mutations in NPC1 or NPC2 gene
- Type A: Hepatosplenomegaly by age 3 months. Fails to thrive. Psychomotor regression. Interstitial lung disease, recurrent lung infections, respiratory failure. Eye cherry-red spot. Death in childhood.
- Type B: mid-childhood. Same as A but less severe. Short stature.
- Type C1/C2: Ataxia, vertical supranuclear gaze palsy, dystonia, severe liver disease, and interstitial lung disease. Dysphagia, intellectual deterioration, seizures
- FBC count: Pancytopenia from hypersplenism
- LFTS: elevated. raised cholesterol (HDL) and TGS
- CXR: reticulonodular shadowing
- PFTS: restrictive lung disease
- Echocardiogram: valve dysfunction
- Measure enzyme activity in peripheral white blood cells or in cultured fibroblasts.
- Genetic Mutation analysis - can be done in utero
- Type A is supportive alone.
- Type B with high cholesterol should have cholesterol-lowering with statins and monitor LFTs. Transfuse bleeding. Oxygen for lung disease.