Sphingolipidoses

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Sphingolipidoses
Classification and external resources
Inborn errors of metabolism.svg
Diagram showing some of the sphingolipidoses
ICD-10E75.3
ICD-9272.7
DiseasesDB33438
MeSHD013106
 
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Sphingolipidoses
Classification and external resources
Inborn errors of metabolism.svg
Diagram showing some of the sphingolipidoses
ICD-10E75.3
ICD-9272.7
DiseasesDB33438
MeSHD013106

Sphingolipidoses are a class of lipid storage disorders relating to sphingolipid metabolism. The main members of this group are Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs disease and [[Metachromatic leukodystrophy]]. They are generally inherited in an [[autosomal recessive]] fashion, but notably Fabry disease is [[X-linked recessive]]. Taken together, sphingolipidoses have an [[incidence (epidemiology)|incidence]] of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly [[Fabry disease]] and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression

 may be mild for juvenile- or adult-onset forms. 

Accumulated products[edit]

Overview[edit]

Table[edit]

Comparison of the main sphingolipidoses
DiseaseDeficient enzyme[1]Accumulated products[1]Symptoms[1]

Inheritance[1] !! Incidence !! Generally accepted

 treatments !! Prognosis 
Niemann-Pick diseaseSphingomyelinaseSphingomyelin in brain and [[red blood

cell|RBC]]s ||

Autosomal recessive1 in 100,000[2]LimitedUsually fatal by the age of approx 1.5

years.[3]

Fabry diseaseα-galactosidase AGlycolipids, particularly ceramide

trihexoside, in brain, heart, kidney ||

X-linked[4]Between 1 in 40,000 to 1 in 120,000 live births for

males.[5]

Enzyme replacement therapy (but expensive)Life expectancy among males of approximately 60

years.[6]

Krabbe diseaseGalactocerebrosidaseGlycolipids, particularly

galactocerebroside, in oligodendrocytes ||

Autosomal recessiveAbout 1 in 100,000 births.[7]LimitedGenerally fatal before age 2 for infants
Gaucher diseaseGlucocerebrosidaseGlucocerebrosides in RBCs, liver and

spleen ||

Autosomal recessiveAbout 1 in 20,000 live

births,[8]

 more among Ashkenazi Jews  
Enzyme replacement therapy (but expensive)May live well into adulthood
Tay-Sachs diseaseHexosaminidase AGM2 gangliosides in neurons
  • Neurodegeneration
  • Developmental disability
  • Early death
Autosomal recessiveApproximately 1 in 320,000 newborns in the general

population,[9] more in Ashkenazi Jews

NoneDeath by approx. 4 years for infantile Tay–Sachs [10]
Metachromatic leukodystrophy (MLD)Arylsulfatase A or prosaposinSulfatide compounds in

neural tissue || Demyelinisation in CNS and PNS:

  • Mental retardation
  • Motor dysfunction
  • Ataxia
  • Hyporeflexia
  • Seizures
Autosomal recessive[11]1 in 40,000 to 1 in 160,000[12]NoneDeath by approx. 5 years for infantile MLD

Metabolic pathways[edit]

Sphingolipidoses.svg

See also[edit]

References[edit]

  1. ^ a b c d If not otherwise specified, reference is: Marks, Dawn B.; Swanson, Todd; Sandra I Kim; Marc Glucksman (2007). Biochemistry and molecular biology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 0-7817-8624-X. 
  2. ^ [http://ghr.nlm.nih.gov/condition/niemann-pick-disease Niemann-Pick disease] from Genetics Home Reference. Reviewed: January 2008. Based on an incidence in a general population of 1 in 250,000 for types A and B and 1 in 150,000 for type C
  3. ^ [http://www.ninds.nih.gov/disorders/niemann/niemann.htm NINDS Niemann-Pick Disease Information Page] at the National Institute of Neurological Disorders and Stroke. Last updated October 6, 2011
  4. ^ Banikazemi M, Desnick RJ, Astrin KH (2009-07-08). "Fabry Disease". eMedicine Pediatrics: Genetics and Metabolic Disease. Medscape. Retrieved 2010-12-31. 
  5. ^ {{cite doi|10.1111/j.1365-2362.2004.01309.x}}
  6. ^ Waldek, S.; Patel, M. R.; Banikazemi, M.; Lemay, R.; Lee, P. (2009). "Life expectancy and cause of death in males and females with Fabry disease: Findings from the Fabry Registry". Genetics in Medicine 11 (11): 790–796. doi:10.1097/GIM.0b013e3181bb05bb. PMID 19745746.  edit
  7. ^ "Krabbe disease". Genetics Home Reference. [[United States National Library of Medicine]]. 2008-05-02. Retrieved 2008-05-07. 
  8. ^ [http://www.gaucherdisease.org/what_is.php Gaucher Disease] at National Gaucher Foundation. Retrieved June 2012
  9. ^ [http://emedicine.medscape.com/article/951943-overview GM2 Gangliosidoses - Introduction And Epidemiology] at Medscape. Author: David H Tegay. Updated: Mar 9, 2012
  10. ^ Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert (2010). "Impact of Gene Patents and Licensing Practices on Access to Genetic Testing and Carrier Screening for Tay–Sachs and Canavan Disease". Genetics in medicine : Official journal of the American College of Medical Genetics 12 (4 Suppl): S5–S14. doi:10.1097/GIM.0b013e3181d5a669. PMC 3042321. PMID 20393311. 
  11. ^ Gieselmann V, Zlotogora J, Harris A, Wenger DA, Morris CP (1994). "Molecular genetics of metachromatic leukodystrophy". Hum. Mutat. 4 (4): 233–42. doi:10.1002/humu.1380040402. PMID 7866401. 
  12. ^ [http://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy Metachromatic leukodystrophy] at Genetics Home Reference. Reviewed September 2007

External links[edit]