Niemann-Pick Disease

Niemann-Pick disease is a sphingolipidosis, an inherited disorder of metabolism, caused by deficient sphingomyelinase activity, resulting in accumulation of sphingomyelin (ceramide phosphorylcholine) in reticuloendothelial cells. Diagnosis is by DNA analysis and/or enzyme analysis of white blood cells. Bone marrow transplantation, stem cell transplantation, and enzyme replacement may be treatment options.

For more information, see table Some Sphingolipidoses and see table Other Lipidoses.

See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.

Niemann-Pick disease inheritance is autosomal recessive and appears most often in people of Ashkenazi Jewish ancestry; 2 types, A and B, exist. Type C Niemann-Pick disease is an unrelated enzymatic defect involving abnormal cholesterol storage.

Children with type A have < 5% of normal sphingomyelinase activity. The disease is characterized by hepatosplenomegaly, failure to thrive, and rapidly progressive neurodegeneration. Death occurs by age 2 or 3 years.

Patients with type B have sphingomyelinase activity within 5 to 10% of normal. Type B is more variable clinically than type A. Hepatosplenomegaly and lymphadenopathy may occur. Pancytopenia is common. Most patients with type B have little or no neurologic involvement, may have intellectual disability, and survive into adulthood; they may be clinically indistinguishable from those with type I Gaucher disease. In severe cases of type B, progressive pulmonary infiltrates cause major complications.

Children with type C develop symptoms usually during childhood, with seizures and neurologic deterioration. Type C is always fatal, and most children die before age 20.