Niemann-Pick Disease

Genetics / Neurology

Overview

Definition

A group of autosomal recessive lysosomal storage disorders characterized by sphingomyelinase deficiency (Types A/B) or impaired lipid trafficking (Type C).

Epidemiology

Rare, Type A is highly lethal in early infancy.

Etiology & Risk Factors

  • SMPD1 mutations (Types A/B) or NPC1/NPC2 mutations (Type C)

Clinical Symptoms

  • Hepatosplenomegaly
  • Progressive neurological regression
  • Cherry-red spot on macula (Type A)
  • Vertical supranuclear gaze palsy (Type C)

Clinical Approach

Diagnosis

  • Acid sphingomyelinase activity (Types A/B)
  • Filipin staining of skin fibroblasts (Type C)
  • Genetic testing

Management

  • Symptomatic care
  • Miglustat for neurological symptoms in Type C

Complications

  • Severe developmental delay / Dementia
  • Respiratory failure
  • Hepatic failure