Niemann-Pick disease type B

Definition: NPD type B is a rare inborn error of metabolism of autosomal recessive inheritance. Patients with Niemann-Pick disease type B (NPDB) have a benign course and prognosis. It is mainly a visceral form without neurologic manifestations despite the massive visceral involvement. NPDB is caused by mutations in the acid lysosomal sphingomyelin phosphodiesterase-1 gene (SMPD1) (MIM.607608)

Digital slides

 Case 52 (HPC:52) : Liver in Niemann-Pick disease type B (NPDB)
 Case 129 (HPC:129) : Lung and liver in Niemann-Pick disease type B (NPDB)

Morphological synopsis

 foamy resident cells and histiocytes in several organs as lung, liver, spleen, kidney.

• microvacuolated hepatocytes (hepatic microsteatosis)

 large vacuolated foam cells (’NP cells’) on bone marrow biopsy
 sea blue histiocytes
 decreased platelets

Clinical synopsis

Patients with Niemann-Pick disease type B (NPDB) have a benign course and prognosis, while Niemann-Pick disease type A (NPDA) and Niemann-Pick disease type C (NPDC) are always associated with severe neurological involvement. They are known to be complicated with varying degrees of prognosis-determining liver dysfunction. It is mainly a visceral form without neurologic manifestations despite the massive visceral involvement.

 Onset in infancy or childhood
 Variable phenotype
 More common in Ashkenazi Jews
 Allelic disorder to Niemann-Pick disease type A (MIM.257200)
 short stature (less common)
 cherry-red maculae (less common)
 dyspnea
 frequent respiratory infections
 decreased pulmonary diffusion secondary to alveolar infiltration
 diffuse reticular or finely nodular infiltrations
 hepatomegaly
 progressive liver failure (7655746)
  splenomegaly
 absence of neurologic manifestations

Associations

 generalized AL amyloidosis of kappa type (7655746)

Ultrastructure

 foam cells with lamellar inclusions

Laboratory

 Decreased acid sphingomyelinase activity
 Increased LDL cholesterol
 Increased triglycerides
 Decreased HDL cholesterol

Etiology

 Caused by mutations in the acid lysosomal sphingomyelin phosphodiesterase-1 gene (SMPD1) (MIM.607608)

See also

 lysosomal storage diseases
 Niemann-Pick diseases (NPDs)

• Niemann-Pick disease type A (NPDA)
• Niemann-Pick disease type B (NPDB)
• Niemann-Pick disease type C (NPDC)

References

 Liver and Skin Histopathology in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B). Thurberg BL, Wasserstein MP, Schiano T, O’Brien F, Richards S, Cox GF, McGovern MM. Am J Surg Pathol. 2012 Aug;36(8):1234-46. PMID: 22613999

 Takahashi T, Akiyama K, Tomihara M, Tokudome T, Nishinomiya F, Tazawa Y, Horinouchi K, Sakiyama T, Takada G. Heterogeneity of liver disorder in type B Niemann-Pick disease. Hum Pathol. 1997 Mar;28(3):385-8. PMID: 9042807