H00424 | |
H number | H00424 |
Name | Defects in the degradation of sphingomyelin |
Description | Defects in the degradation of sphingomyelin are a group of autosomal recessive lysosomal storage diseases including Niemann-Pick disease (NPD), type A/B and Farber lipogranulomatosis. NPD is 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. |
Category | Inherited metabolic disorder, Lysosomal disease |
Network | - |
Gene | (NPD) SMPD1 [HSA:6609] [KO:K12350] (Farber) ASAH1 [HSA:427] [KO:K12348] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | - |
Comment | 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. |
Other DBs | ICD-11: 5C56.0Y ICD-10: E75.2 OMIM: 257200 607616 228000 |
Reference | PMID:18567738 AUTHORS Smith EL, Schuchman EH TITLE The unexpected role of acid sphingomyelinase in cell death and the pathophysiology of common diseases. JOURNAL FASEB J 22:3419-31 (2008) DOI:10.1096/fj.08-108043 PMID:18708002 AUTHORS Heese BA TITLE Current strategies in the management of lysosomal storage diseases. JOURNAL Semin Pediatr Neurol 15:119-26 (2008) DOI:10.1016/j.spen.2008.05.005 PMID:17632693 AUTHORS Schuchman EH TITLE The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. JOURNAL J Inherit Metab Dis 30:654-63 (2007) DOI:10.1007/s10545-007-0632-9 PMID:10760463 AUTHORS Ridgway ND TITLE Interactions between metabolism and intracellular distribution of cholesterol and sphingomyelin. JOURNAL Biochim Biophys Acta 1484:129-41 (2000) DOI:10.1016/S1388-1981(00)00006-8 PMID:19944693 (NPC) AUTHORS Schuchman EH TITLE Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease. JOURNAL FEBS Lett 584:1895-900 (2010) DOI:10.1016/j.febslet.2009.11.083 PMID:17064658 (Farber) AUTHORS Park JH, Schuchman EH TITLE Acid ceramidase and human disease. JOURNAL Biochim Biophys Acta 1758:2133-8 (2006) DOI:10.1016/j.bbamem.2006.08.019 PMID:11241842 (Farber) AUTHORS Bar J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K TITLE Molecular analysis of acid ceramidase deficiency in patients with Farber disease. JOURNAL Hum Mutat 17:199-209 (2001) DOI:10.1002/humu.5 |