# Sphingolipidoses

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**Sphingolipidoses** are a class of [lipid storage disorders](/source/Lipid_storage_disorders) or degenerative storage disorders caused by deficiency of an enzyme that is required for the [catabolism](/source/Catabolism) of lipids that contain [ceramide](/source/Ceramide),[1] also relating to [sphingolipid](/source/Sphingolipid) metabolism. The main members of this group are [Niemann–Pick disease](/source/Niemann%E2%80%93Pick_disease), [Fabry disease](/source/Fabry_disease), [Krabbe disease](/source/Krabbe_disease), [Gaucher disease](/source/Gaucher_disease), [Tay–Sachs disease](/source/Tay%E2%80%93Sachs_disease) and [metachromatic leukodystrophy](/source/Metachromatic_leukodystrophy). They are generally inherited in an [autosomal recessive](/source/Autosomal_recessive) fashion, but notably Fabry disease is [X-linked recessive](/source/X-linked_recessive). Taken together, sphingolipidoses have an [incidence](/source/Incidence_(epidemiology)) of approximately 1 in 10,000, but substantially more in certain populations such as [Ashkenazi Jews](/source/Ashkenazi_Jews). [Enzyme replacement therapy](/source/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

- [Gangliosides](/source/Gangliosides): [Gangliosidosis](/source/Gangliosidosis) - [GM1 gangliosidoses](/source/GM1_gangliosidoses) - [GM2 gangliosidoses](/source/GM2_gangliosidoses) - [Tay–Sachs disease](/source/Tay%E2%80%93Sachs_disease) - [Sandhoff disease](/source/Sandhoff_disease) - [GM2-gangliosidosis, AB variant](/source/GM2-gangliosidosis,_AB_variant)
- [Glycolipids](/source/Glycolipid) - [Fabry's disease](/source/Fabry's_disease) - [Krabbe disease](/source/Krabbe_disease) - [Metachromatic leukodystrophy](/source/Metachromatic_leukodystrophy)
- [Glucocerebrosides](/source/Glucocerebroside) - [Gaucher's disease](/source/Gaucher's_disease)

## Comparison

Comparison of the main sphingolipidoses Disease Deficient enzyme[2] Accumulated products[2] Symptoms[2] Inheritance[2] Incidence Generally accepted treatments Prognosis Niemann-Pick disease Sphingomyelinase Sphingomyelin in brain and RBCs Mental retardation Spasticity Seizures Hepatosplenomegaly Thrombocytopenia Ataxia Autosomal recessive 1 in 100,000[3] Limited Highly variable, infantile neurovisceral Niemann Pick disease (Type A ASMD) is usually fatal before 3 years of age. Estimasted mortality before adulthood for the Chronic visceral form (type B) is around 15-25%. Many live well into adulthood and may reach a normal lifespan. Diagnosis have been made in the 7th decade of life.[4][5][6] Fabry disease α-galactosidase A Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney Ischemic infarction in affected organs Acroparesthesia Angiokeratomas hypohidrosis X-linked[7] Between 1 in 40,000 to 1 in 120,000 live births for males[8] Enzyme replacement therapy (but expensive) Life expectancy among males of approximately 60 years[9] Krabbe disease Galactocerebrosidase Glycolipids, particularly galactocerebroside, in oligodendrocytes Spasticity Neurodenegeration (leading to death) Hypertonia Hyperreflexia Decerebration-like posture Blindness Deafness Autosomal recessive About 1 in 100,000 births[10] Bone marrow transplant (high risk, potential failure, effectively provides enzyme replacement to the central nervous system from six months post-transplant, if done in the earliest stages; less effective enzyme replacement provision for the peripheral nervous system) Untransplanted, and in the case of a failed transplant, generally fatal before age 2 for infants Gaucher disease Glucocerebrosidase Glucocerebrosides in RBCs, liver and spleen Hepatosplenomegaly Pancytopenia Bone pain Erlenmeyer flask deformity Autosomal recessive About 1 in 20,000 live births,[11] more among Ashkenazi Jews Enzyme replacement therapy (but expensive) May live well into adulthood Tay–Sachs disease Hexosaminidase A GM2 gangliosides in neurons Neurodegeneration Developmental disability Early death Autosomal recessive Approximately 1 in 320,000 newborns in the general population,[12] more in Ashkenazi Jews None Death by approx. 4 years for infantile Tay–Sachs[13] Metachromatic leukodystrophy (MLD) Arylsulfatase A or prosaposin Sulfatide compounds in neural tissue Demyelination in CNS and PNS: Intellectual disability Motor dysfunction Ataxia Hyporeflexia Seizures Autosomal recessive[14] 1 in 40,000 to 1 in 160,000[15] Bone marrow transplant (high risk, potential failure, effectively provides enzyme replacement to the central nervous system from six months post-transplant, if done in the earliest stages; less effective enzyme replacement provision for the peripheral nervous system) Untransplanted, and in the case of a failed transplant, death by approx. 5 years for infantile MLD

## See also

- [Lipid storage disorder](/source/Lipid_storage_disorder)

## References

1. Lynn, D. Joanne, Newton, Herbert B. and Rae-Grant, Alexander D. eds. 5-Minute Neurology Consult, The. 2nd Edition. Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103 USA: Lippincott Williams & Wilkins, 2012. Books@Ovid. Web. 03 December, 2020

1. If not otherwise specified, reference is: Marks, Dawn B.; Swanson, Todd; Sandra I Kim; Marc Glucksman (2007). [*Biochemistry and molecular biology*](https://archive.org/details/biochemistrymole0000swan_f9p0). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-0-7817-8624-9.

1. [Niemann-Pick disease](https://medlineplus.gov/genetics/condition/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

1. Uz E, Cipil H, Turgut FH, Kaya A, Kargili A, Bavbek N, Ali A, Ali K. Niemann-Pick disease type B presenting with hepatosplenomegaly and thrombocytopenia. South Med J. 2008 Nov;101(11):1188. doi: 10.1097/SMJ.0b013e3181836b4c. PMID 19088546.

1. McGovern MM, Lippa N, Bagiella E, Schuchman EH, Desnick RJ, Wasserstein MP. Morbidity and mortality in type B Niemann-Pick disease. Genet Med 2013;15:618–623.

1. Cassiman D, Packman S, Bembi B, et al. Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (NiemannPick disease type B and B variant): Literature review and report of new cases. Mol Genet Metab 2016;118:206–213.

1. Banikazemi M, Desnick RJ, Astrin KH (2009-07-08). ["Fabry Disease"](http://emedicine.medscape.com/article/951451-overview). *eMedicine Pediatrics: Genetics and Metabolic Disease*. Medscape. Retrieved 2010-12-31.

1. 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](https://doi.org/10.1111/j.1365-2362.2004.01309.x). [PMID 15025684](https://pubmed.ncbi.nlm.nih.gov/15025684)

1. 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](https://doi.org/10.1097/GIM.0b013e3181bb05bb). [PMID 19745746](https://pubmed.ncbi.nlm.nih.gov/19745746)

1. ["Krabbe disease"](https://web.archive.org/web/20040407040718/http://ghr.nlm.nih.gov/condition=krabbedisease). *Genetics Home Reference*. [United States National Library of Medicine](/source/United_States_National_Library_of_Medicine). 2008-05-02. Archived from [the original](http://ghr.nlm.nih.gov/condition=krabbedisease) on April 7, 2004. Retrieved 2008-05-07.

1. [Gaucher Disease](http://www.gaucherdisease.org/what_is.php) at National Gaucher Foundation. Retrieved June 2012

1. [GM2 Gangliosidoses – Introduction And Epidemiology](http://emedicine.medscape.com/article/951943-overview) at Medscape. Author: David H Tegay. Updated: Mar 9, 2012

1. 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*. **12** (4 Suppl): S5–S14. [doi:10.1097/GIM.0b013e3181d5a669](https://doi.org/10.1097/GIM.0b013e3181d5a669). [PMC 3042321](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042321). [PMID 20393311](https://pubmed.ncbi.nlm.nih.gov/20393311)

1. 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](https://doi.org/10.1002/humu.1380040402). [PMID 7866401](https://pubmed.ncbi.nlm.nih.gov/7866401)

1. [Metachromatic leukodystrophy](https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/) at Genetics Home Reference. Reviewed September 2007

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Adapted from the Wikipedia article [Sphingolipidoses](https://en.wikipedia.org/wiki/Sphingolipidoses) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Sphingolipidoses?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.