Pathophysiology

Niemann-Pick disease is an autosomal-recessive lipidosis in which sphingomyelin (i.e., ceramide phosphorylcholine) accumulates in the lysosomes of reticuloendothelial cells.72 Several types have been identified. Types A and B result from a deficiency of acid sphingomyelinase. Types C and D are characterized by abnormal cholesterol esterification and transport out of the lysosome.

Clinical presentation

Type C is most associated with seizures. Two subtypes of type-C Niemann-Pick disease have been identified based on the temporal sequence of neurologic events, neurophysiologic abnormalities, and longevity.73

Neonates with type-C Niemann-Pick disease may be jaundiced at birth. Slowly progressive neurologic deterioration begins within 2 years. Partial, generalized tonic-clonic and atonic seizures may occur and are usually refractory to antiepileptic drugs.73 Hepatosplenomegaly is often present.

Evaluation

Laboratory testing may show pancytopenia from bone marrow infiltration. Sphingomyelinase activity is not reduced, but the cholesterol transport defect can be documented in cell culture.

Treatment

There is currently no specific treatment for any of the Niemann-Pick disease subtypes, and care is supportive.72

Adapted from: Schachter SC and Lopez MR. Metabolic disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;195–208. 
With permission from Elsevier (www.elsevier.com)

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Reviewed By: 
Steven C. Schachter, MD
on: 
Thursday, April 1, 2004