KEGG   DISEASE: Defects in the degradation of sphingomyelin
Entry
H00424                      Disease                                

Name
Defects in the degradation of sphingomyelin
  Subgroup
Niemann-Pick disease (NPD), type A/B [DS:H00137]
Farber lipogranulomatosis [DS:H00138]
  Supergrp
Sphingolipidosis [DS:H00423]
Lysosomal storage disease [DS:H01425]
Description
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.
Category
Inherited metabolic disease; Lysosomal storage disease; Nervous system disease
Brite
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Lysosomal storage diseases
   H00424  Defects in the degradation of sphingomyelin
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Inborn errors of metabolism
    5C56  Lysosomal diseases
     H00424  Defects in the degradation of sphingomyelin
Pathway
hsa00600  Sphingolipid metabolism
hsa04142  Lysosome
Gene
(NPD) SMPD1, ASM; sphingomyelin phosphodiesterase [HSA:6609] [KO:K12350]
(Farber) ASAH1; acid ceramidase [HSA:427] [KO:K12348]
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
  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
Reference
  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
Reference
  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
Reference
  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
Reference
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
Reference
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
Reference
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

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