The Niemann-Pick diseases

Edward H. Schuchman, Robert J. Desnick

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Two distinct metabolic derangements are included under the eponym “Niemann-Pick disease (NPD)". The first is due to the deficient activity of the lysosomal enzyme acid sphingomyelinase (ASM). Patients with this disorder [also referred to as ASM-deficient (ASMD) NPD] are broadly classified as having types A, A/B, and B NPD depending on their degree of neurologic involvement. Type A NPD patients, also known as the infantile neurovisceral form, exhibit hepatosplenomegaly in infancy and profound central nervous system (CNS) involvement. They rarely survive beyond 2-3 years of age. Type B patients, also known as the chronic visceral form, 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 many may survive into adulthood. Patients with phenotypes intermediate between types A and B NPD (type A/B), also known as the chronic neurovisceral form, also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second NPD category are designated as having types C and D NPD. These individuals may have mild hepatosplenomegaly, but the CNS is profoundly affected. Impaired intracellular trafficking of cholesterol causes types C and D NPD, and two distinct gene defects have been found. All type D patients originate from a common Nova Scotian ancestry.

Original languageEnglish
Title of host publicationRosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease
Subtitle of host publicationVolume 1
PublisherElsevier
Pages451-460
Number of pages10
ISBN (Electronic)9780128139554
DOIs
StatePublished - 1 Jan 2020

Keywords

  • Acid sphingomyelinase
  • Cholesterol
  • Enzyme replacement therapy
  • Phenotypic spectrum
  • Sphingomyelin

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