Niemann-Pick disease (type B)

Niemann-Pick type B disease (NPD-B), along with Niemann-Pick type A (NPD-A) disease, is one of the more common forms of this group of autosomal recessive disorders that share the feature of abnormal storage of sphingomyelin. Common manifestation include splenomegaly and variable neurologic deficits. It is caused by mutations in the sphingomyelin phosphodiesterase-1 gene (SMDPD-1).

NPD-B is pan-ethnic, unlike NPD-A which is much more common in Ashkenazi jews. It's onset is usually in late childhood and is much less severe than NPD-A, with a good prognosis of survival into adulthood.

The disease is characterized by hepatosplenomegaly during infancy and the majority of patients will develop thrombocytopenia due to hypersplenism.

In the liver, the infiltration of foamy cells and ballooning of hepatocytes can lead to various degrees of hepatic fibrosis.

Contrary to NPD-A, patients with NPD-B have very little or no central nervous system impairment. In patients who live long enough, however, neurologic disorders such as nystagmus, psychiatric disease and peripheral neuropathy may occur.

Other clinical features include:

  • interstitial lung disease
  • short stature with delayed skeletal maturation
  • ocular abnormalities (cherry red maculae)
  • hyperlipidemia (which can lead to early onset vascular disease)

The definitive diagnosis of those diseases (NPD-A and B) is based in the demonstration of residual acid sphingomyelinase activity in peripheral blood leukocytes to be <10 percent of controls.

SMPD1 mutation can also be evaluated by genetic testing, but it has proven to be most effective in patients of Ashkenazi descent (for type A disease) and of North African descent (for type B disease).

Since the exams above are not widely available (especially in developing countries), the combination of blood tests and radiological features below is highly suggestive of this diagnosis:

  • interstitial lung disease
  • hepatosplenomegaly with thrombocytopenia
  • lipid abnormalities in peripheral blood (decreased HDL-c, increased LDL-c, and hypertriglyceridemia)
Plain radiograph
  • chest
    • reticulonodular pattern which usually starts in the lower lobes
    • calcified micronodules
  • skeletal
    • short stature with delayed skeletal maturation
    • osteopenia
CT
  • chest
    • smooth interlobular and intralobular septal thickening
    • patchy ground glass attenuation (can form "crazy paving")
    • calcified micronodules
    • thymus and other lymphatic organs may be enlarged
  • abdomen
    • hepatosplenomegaly with numerous parenchymal calcifications
    • can lead to cirrhosis and hepatic failure
    • unlike the liver, low-density masses can be seen in the spleen
  • cardiovascular
    • calcified atherosclerotic plaques
MRI
  • central nervous system
    • pronounced cerebellar and mild supratentorial atrophy

Usually these patients suffer from progressive dyspnea due to interstitial lung disease and worsening of hypersplenism. Precocious vascular disease due to adverse lipid profile is also a major cause of mortality.

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Article Information

rID: 43708
Section: Pathology
Tag: cases
Synonyms or Alternate Spellings:
  • Niemann-Pick type B disease (NPD-B)
  • Niemann-Pick disease type B (NPD-B)

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