Niemann-Pick disease type B (NPD-B), along with Niemann-Pick disease type A (NPD-A), is an autosomal recessive disorder due to acid sphingomyelinase deficiency resulting in abnormal storage of sphingomyelin.

Common manifestation of NPD-B includes hepatosplenomegaly, thrombocytopenia, and variable neurologic deficits. It is caused by mutations in the sphingomyelin phosphodiesterase-1 gene (SMDPD1).

Epidemiology

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

Clinical presentation

The disease is characterised 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 ^2,8:

• interstitial lung disease with accumulation of Niemann-Pick cells resulting in an endogenous lipoid pneumonia ⁸

• recurrent respiratory infection

• short stature with delayed skeletal maturation

• ocular abnormalities (cherry red maculae)

• hyperlipidaemia (which can lead to early-onset vascular disease)

Diagnosis

The definitive diagnosis of those diseases (NPD-A and B) is based on the demonstration of residual acid sphingomyelinase activity in peripheral blood leucocytes 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 hypertriglyceridaemia)

Radiographic features

Plain radiograph

• chest

  • reticular or reticulonodular pattern +/- septal lines with a lower lobe predominance ^2,8

  • calcified micronodules ²

• skeletal

  • short stature with delayed skeletal maturation ²

  • osteopenia/osteoporosis ²

CT

• chest

  • smooth interlobular and intralobular septal thickening ^6-8

  • patchy ground-glass attenuation (can form "crazy paving") ^2,7,8

  • lower zone predominance ⁸

  • calcified micronodules ²

  • coronary artery calcification ²

  • thymus may be enlarged ²

• abdomen

  • hepatosplenomegaly (almost always present) ⁵ with numerous parenchymal calcifications

  • can lead to cirrhosis and hepatic failure

  • low-density masses can be seen in the spleen ²

  • adrenal masses ²

• vascular

  • calcified atherosclerotic plaques

MRI

• central nervous system

  • pronounced cerebellar and mild supratentorial atrophy

• skeletal

  • reduced signal in bone marrow ⁵

Treatment and prognosis

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