Types A and B Niemann-Pick disease.
The eponym Niemann-Pick disease (NPD) refers to a group of patients who present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Due to the pioneering work of Roscoe Brady and co-workers, we now know that there are two distinct metabolic abnormalities that account for NPD. The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM; "types A & B" NPD), and the second is due to defective function in cholesterol transport ("type C" NPD). Herein only types A and B NPD will be discussed. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2-3years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings. All patients with types A and B NPD have mutations in the gene encoding ASM (SMPD1), and thus the disease is more accurately referred to as ASM deficiency (ASMD). Herein we will review the clinical, pathological, biochemical, and genetic findings in types A and B NPD, and emphasize the seminal contributions of Dr. Brady to this disease. We will also discuss the current status of therapy for this disorder.
Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, United States. Electronic address: edward.schuchman@mssm.edu.
Edward H
EH
Schuchman
Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, United States.
Robert J
RJ
Desnick
D017668:Age of Onset; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008297:Male; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000145:classification* / Q000235:genetics; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency* / Q000235:genetics
D002784:Cholesterol; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase
Acid sphingomyelinase; Enzyme Replacement Therapy; Mouse model; Niemann-Pick; Sphingomyelin