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Sphingolipidoses
Other namesSphingolipidosis
Diagram showing some of the sphingolipidoses
SpecialtyMedical genetics

Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide,[1] also relating to sphingolipid metabolism. The main members of this group are Niemannโ€“Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tayโ€“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

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Comparison

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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 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 ฮฑ-galactosidase A Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney 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 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 Autosomal recessive About 1 in 20,000 live births,[11] more among Ashkenazi Jews Enzyme replacement therapy (but expensive) May live well into adulthood
Tayโ€“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 Tayโ€“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

Metabolic pathways

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See also

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References

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  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
  2. ^ 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. ISBNย 978-0-7817-8624-9.
  3. ^ 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
  4. ^ 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.
  5. ^ McGovern MM, Lippa N, Bagiella E, Schuchman EH, Desnick RJ, Wasserstein MP. Morbidity and mortality in type B Niemann-Pick disease. Genet Med 2013;15:618โ€“623.
  6. ^ 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;118:206โ€“213.
  7. ^ Banikazemi M, Desnick RJ, Astrin KH (2009-07-08). "Fabry Disease". eMedicine Pediatrics: Genetics and Metabolic Disease. Medscape. Retrieved 2010-12-31.
  8. ^ 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): 236โ€“242. doi:10.1111/j.1365-2362.2004.01309.x. PMIDย 15025684.
  9. ^ 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): 790โ€“796. doi:10.1097/GIM.0b013e3181bb05bb. PMIDย 19745746.
  10. ^ "Krabbe disease". Genetics Home Reference. United States National Library of Medicine. 2008-05-02. Archived from the original on April 7, 2004. Retrieved 2008-05-07.
  11. ^ Gaucher Disease at National Gaucher Foundation. Retrieved June 2012
  12. ^ GM2 Gangliosidoses โ€“ Introduction And Epidemiology at Medscape. Author: David H Tegay. Updated: Mar 9, 2012
  13. ^ Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert (2010). "Impact of Gene Patents and Licensing Practices on Access to Genetic Testing and Carrier Screening for Tayโ€“Sachs and Canavan Disease". Genetics in Medicine. 12 (4 Suppl): S5โ€“S14. doi:10.1097/GIM.0b013e3181d5a669. PMCย 3042321. PMIDย 20393311.
  14. ^ Gieselmann V, Zlotogora J, Harris A, Wenger DA, Morris CP (1994). "Molecular genetics of metachromatic leukodystrophy". Hum. Mutat. 4 (4): 233โ€“42. doi:10.1002/humu.1380040402. PMIDย 7866401.
  15. ^ Metachromatic leukodystrophy at Genetics Home Reference. Reviewed September 2007
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๐Ÿ“š Artikel Terkait di Wikipedia

Lipid storage disorder

Many lipid storage disorders can be classified into the subgroup of sphingolipidoses, as they relate to sphingolipid metabolism. Members of this group include

Sphingolipid

play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on

Lysosomal storage disease

(including Tayโ€“Sachs disease (E75.0-E75.1) - they are a subtype of sphingolipidoses Sphingolipidoses that are not gangliosidoses, including Gaucher's and Niemannโ€“Pick

Sphingosine

then solely formed via degradation of sphingolipid in the lysosome. Sphingolipidoses General structures of sphingolipids Dimethylsphingosine Fingolimod

Glycolipid

glycans from glycolipids to turn them back into unmodified lipids. Sphingolipidoses are a group of diseases that are associated with the accumulation of

Metachromatic leukodystrophy

commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect

GM2 (ganglioside)

gangliosidoses such as Tayโ€“Sachs disease. Ganglioside GM2 activator protein Sphingolipidoses Structures of GM1, GM2, GM3 gangliosides Guetta E, Peleg L (2008).

Gaucher's disease

Sphingolipidoses