Defects in the degradation of sphingomyelin

Niemann-Pick disease (NPD), type A/B [DS:H00137]
Farber lipogranulomatosis [DS:H00138]

Sphingolipidosis [DS:H00423]
Lysosomal storage disease [DS:H01425]

Defects in the degradation of sphingomyelin is a group of autosomal recessive lysosomal storage diseases including Niemann-Pick disease (NPD), type A/B and Farber lipogranulomatosis. NPD caused by deficient acid sphingomyelinase (ASM) activity, and Farber lipogranulomatosis is caused by acid ceramidase deficiency, resulting in accumulation of sphingomyelin, ceramide and cholesterol in many organs. ASM and acid ceramidase are key enzymes of the two steps degradation of sphingomyelin and play important roles in normal membrane turnover.

Inherited metabolic disease; Lysosomal storage disease; Nervous system disease

(NPD) SMPD1, ASM; sphingomyelin phosphodiesterase [HSA:6609] [KO:K12350]
(Farber) ASAH1; acid ceramidase [HSA:427] [KO:K12348]

NPD typeA is the infantile form characterized by a rapidly progressive neurodegenerative course that leads to early death. NPD typeB is the later-onset form in which patients exhibit little or no neurological symptoms, but may have severe and progressive visceral organ abnormalities, including hepatosplenomegaly and cardiovascular disease. The different clinical presentations of Types A and B NPD are likely due to small differences in the amount of residual, functional ASM activity.

PMID:18567738

Smith EL, Schuchman EH

The unexpected role of acid sphingomyelinase in cell death and the pathophysiology of common diseases.

FASEB J 22:3419-31 (2008)
DOI:10.1096/fj.08-108043

PMID:18708002

Heese BA

Current strategies in the management of lysosomal storage diseases.

Semin Pediatr Neurol 15:119-26 (2008)
DOI:10.1016/j.spen.2008.05.005

PMID:17632693

Schuchman EH

The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease.

J Inherit Metab Dis 30:654-63 (2007)
DOI:10.1007/s10545-007-0632-9

PMID:10760463

Ridgway ND

Interactions between metabolism and intracellular distribution of cholesterol and sphingomyelin.

Biochim Biophys Acta 1484:129-41 (2000)
DOI:10.1016/S1388-1981(00)00006-8

PMID:19944693 (NPC)

Schuchman EH

Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease.

FEBS Lett 584:1895-900 (2010)
DOI:10.1016/j.febslet.2009.11.083

PMID:17064658 (Farber)

Park JH, Schuchman EH

Acid ceramidase and human disease.

Biochim Biophys Acta 1758:2133-8 (2006)
DOI:10.1016/j.bbamem.2006.08.019

PMID:11241842 (Farber)

Bar J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K

Molecular analysis of acid ceramidase deficiency in patients with Farber disease.

Hum Mutat 17:199-209 (2001)
DOI:10.1002/humu.5