Sphingolipidoses (singular "sphingolipidosis") 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 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 ]
Comparison of the main sphingolipidoses
[1 ] Accumulated products
[1 ] Symptoms
[1 ] Inheritance
[1 ] Incidence
Generally accepted treatments
Sphingomyelin in brain and RBCs
1 in 100,000
[2 ] Limited
Usually fatal by the age of approx 1.5 years.
Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney
[4 ] Between 1 in 40,000 to 1 in 120,000 live births for males.
Enzyme replacement therapy (but expensive)
Life expectancy among males of approximately 60 years. [6 ]
Galactocerebrosidase Glycolipids, particularly galactocerebroside, in
About 1 in 100,000 births.
[7 ] Limited
Generally fatal before age 2 for infants
Glucocerebrosides in RBCs, liver and spleen
About 1 in 20,000 live births,
more among [8 ] Ashkenazi Jews
Enzyme replacement therapy (but expensive) May live well into adulthood
GM2 gangliosides in neurons
Approximately 1 in 320,000 newborns in the general population,
more in Ashkenazi Jews [9 ] None
Death by approx. 4 years for infantile Tay–Sachs
Metachromatic leukodystrophy (MLD)
Arylsulfatase A or prosaposin
Sulfatide compounds in neural tissue Demyelinisation in
CNS and PNS:
[11 ] 1 in 40,000 to 1 in 160,000
[12 ] None
Death by approx. 5 years for infantile MLD
Metabolic pathways [ edit ]
See also [ edit ]
References [ edit ]
^ 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.
^ 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
^ NINDS Niemann-Pick Disease Information Page at the National Institute of Neurological Disorders and Stroke. Last updated October 6, 2011
^ Banikazemi M, Desnick RJ, Astrin KH (2009-07-08). "Fabry Disease". eMedicine Pediatrics: Genetics and Metabolic Disease. Medscape . Retrieved . 2010-12-31
^ Mehta, A.; Ricci, R.; Widmer, U.; Dehout, F.; Garcia De Lorenzo, A.; Kampmann, C.; Linhart, A.; Sunder-Plassmann, G.; Ries, M.; Beck, M. (2004). "Fabry disease defined: Baseline clinical manifestations of 366 patients in the Fabry Outcome Survey". European Journal of Clinical Investigation 34 (3): 236–242. doi: 10.1111/j.1365-2362.2004.01309.x. PMID 15025684.
^ 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.
^ "Krabbe disease". Genetics Home Reference. United States National Library of Medicine. 2008-05-02 . Retrieved . 2008-05-07
^ Gaucher Disease at National Gaucher Foundation. Retrieved June 2012
^ GM2 Gangliosidoses - Introduction And Epidemiology at Medscape. Author: David H Tegay. Updated: Mar 9, 2012
^ 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.
^ 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.
^ Metachromatic leukodystrophy at Genetics Home Reference. Reviewed September 2007
External links [ edit ]