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,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 also 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 Gangliosides: Gangliosidosis GM1 gangliosidoses GM2 gangliosidoses Tay–Sachs disease Sandhoff disease GM2-gangliosidosis, AB variant Glycolipids Fabry's disease Krabbe disease Metachromatic leukodystrophy Glucocerebrosides Gaucher's disease
Comparison +Comparison of the main sphingolipidoses Disease Deficient enzymeIf not otherwise specified, reference is: Accumulated products Symptoms Inheritance 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 100,000Niemann-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 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.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.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.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. Fabry disease α-galactosidase A Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney Ischemic infarction in affected organs Acroparesthesia Angiokeratomas hypohidrosis X-linked 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 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 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,Gaucher Disease at National Gaucher Foundation. Retrieved June 2012 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,GM2 Gangliosidoses – Introduction And Epidemiology at Medscape. Author: David H Tegay. Updated: Mar 9, 2012 more in Ashkenazi Jews None Death by approx. 4 years for infantile Tay–Sachs 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 1 in 40,000 to 1 in 160,000Metachromatic leukodystrophy at Genetics Home Reference. Reviewed September 2007 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 Lipid storage disorder
References
External links