Sphingolipidoses

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Sphingolipidoses
Other namesSphingolipidosis
Diagram showing some of the sphingolipidoses
SpecialtyMedical genetics

Sphingolipidoses are a class of

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

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 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
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:
  • Mental retardation
  • 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

See also

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
  2. ^
    ISBN 0-7817-8624-X
    .
  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;15:618–623.
  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;118:206–213.
  7. ^ Banikazemi M, Desnick RJ, Astrin KH (2009-07-08). "Fabry Disease". eMedicine Pediatrics: Genetics and Metabolic Disease. Medscape. Retrieved 2010-12-31.
  8. PMID 15025684
    .
  9. PMID 19745746
    .
  10. ^ "Krabbe disease". Genetics Home Reference. United States National Library of Medicine. 2008-05-02. Retrieved 2008-05-07.
  11. ^ Gaucher Disease at National Gaucher Foundation. Retrieved June 2012
  12. ^ GM2 Gangliosidoses – Introduction And Epidemiology at Medscape. Author: David H Tegay. Updated: Mar 9, 2012
  13. PMID 20393311
    .
  14. PMID 7866401
    .
  15. ^ Metachromatic leukodystrophy at Genetics Home Reference. Reviewed September 2007

External links

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