2-Hydroxyglutaric aciduria

2-Hydroxyglutaric aciduria Alpha-hydroxyglutaric acid.png Alpha-Hydroxyglutaric acid 2-hydroxyglutaric aciduria is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in one's urine. It is either autosomal recessive or autosomal dominant.Reference Genetics Home 2-hydroxyglutaric aciduria https://medlineplus.gov/genetics/condition/2-hydroxyglutaric-aciduria/ 25 January 2017 Genetics Home Reference en Presentation The signs/symptoms of this condition are consistent with the following:L-2-hydroxyglutaric aciduria Genetic and Rare Diseases Information Center (GARD) – an NCATS Program https://rarediseases.info.nih.gov/diseases/10472/l-2-hydroxyglutaric-aciduria 25 January 2017 rarediseases.info.nih.gov en Intellectual disability, Muscular hypotonia Encephalitis Seizures Aphasia Cause thumb|right|Most forms of 2-Hydroxyglutaric aciduria have an autosomal recessive pattern of inheritance.Mutation in several genes can lead to different types of 2-hydroxyglutaric aciduria. For example, the D2HGDH and L2HGDH genes provide instructions for making enzymes that are found in mitochondria - in which these enzymes break down D-2-hydroxyglutarate and L-2-hydroxyglutarate, respectively, as a part of normal reaction series that generate energy for cell activities. Any mutations occur in either of these genes would interrupt the functional enzymes and allow both 2-hydroxyglutarates to accumulate in cells, which cause 2-hydroxyglutaric aciduria type I. Moreover, it is known that type II for D-2-hydroxyglutaric aciduria and a mixed type for both 2-hydroxyglutarates come from mutations in IDH2 gene and SLC25A1 gene, respectively.2-hydroxyglutaric aciduria: MedlinePlus Genetics https://medlineplus.gov/genetics/condition/2-hydroxyglutaric-aciduria/ 2022-07-17 medlineplus.gov enKranendijk Martijn Struys Eduard A. Salomons Gajja S. Van der Knaap Marjo S. Jakobs Cornelis 2012 Progress in understanding 2-hydroxyglutaric acidurias Journal of Inherited Metabolic Disease 35 4 571–587 10.1007/s10545-012-9462-5 0141-8955 3388262 22391998 Diagnosis Classification 2-hydroxyglutaric aciduria is an organic aciduria, and because of the stereoisomeric property of 2-hydroxyglutarate different variants of this disorder are distinguished: L-2-hydroxyglutaric aciduria The L-2 form is more common, severe, and mainly affects the central nervous system. The basal ganglia are affected, and cystic cavitations in the white matter of the brain are common, beginning in infancy. This form is chronic, with early symptoms such as hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.Seijo-Martinez M, Navarro C, Castro del Rio M, Vila O, Puig M, Ribes A, Butron M 2005 L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings Arch. Neurol. 62 4 666–670 10.1001/archneur.62.4.666 15824270 free It is associated with L2HGDH, which encodes L-2-hydroxyglutarate dehydrogenase.etal Topçu M, Jobard F, Halliez S November 2004 L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1 Hum. Mol. Genet. 13 22 2803–11 10.1093/hmg/ddh300 15385440 free 11655/14532 free L-2-hydroxyglutarate is produced by promiscuous action of malate dehydrogenase on 2-oxoglutarate, and L-2-hydroxyglutarate dehydrogenase is an example of a metabolite repair enzyme that oxidizes L-2-hydroxyglutarate back to 2-oxoglutarate.Van Schaftingen E. Rzem R. Veiga-da-Cunha M. 2009-04-01 L: -2-Hydroxyglutaric aciduria, a disorder of metabolite repair Journal of Inherited Metabolic Disease 32 2 135–142 10.1007/s10545-008-1042-3 1573-2665 19020988 27702186 D-2-hydroxyglutaric aciduria The D2 form is rare, with symptoms including macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness.Nyhan WL, Shelton GD, Jakobs C, Holmes B, Bowe C, Curry CJ, Vance C, Duran M, Sweetman L 1995 D-2-hydroxyglutaric aciduria J. Child Neurol. 10 2 137–142 10.1177/088307389501000216 7782605 19395651 It is caused by recessive mutations in D2HGDHStruys EA, Salomons GS, Achouri Y, Van Schaftingen E, Grosso S, Craigen WJ, Verhoeven NM, Jakobs C Jan 2005 Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria Am J Hum Genet 76 2 358–60 10.1086/427890 1196381 15609246 (type I) or by dominant gain-of-function mutations in IDH2etal Kranendijk M, Struys EA, van Schaftingen E 2010 IDH2 mutations in patients with D-2-hydroxyglutaric aciduria Science 330 6002 336 2010Sci...330..336K 10.1126/science.1192632 20847235 206527781 (type II). Combined D-2- and L-2-hydroxyglutaric aciduria The combined form is characterized by severe early-onset epileptic encephalopathy and absence of developmental progress.etal Muntau A, Röschinger W, Merkenschlager A, van der Knaap MS 2000 Combined D-2- and L-2-hydroxyglutaric aciduria with neonatal onset encephalopathy: a third biochemical variant of 2-hydroxyglutaric aciduria? Neuropediatrics 31 3 137–40 10.1055/s-2000-7497 10963100 It is caused by recessive mutations in SLC25A1 encoding the mitochondrial citrate carrier.Nota B etal 2013 Deficiency in SLC25A1, Encoding the Mitochondrial Citrate Carrier, Causes Combined D-2- and L-2-Hydroxyglutaric Aciduria. The American Journal of Human Genetics 92 4 627–631 10.1016/j.ajhg.2013.03.009 3617390 23561848 Treatment The treatment of 2-Hydroxyglutaric aciduria is based on seizure control, the prognosis depends on how severe the condition is.D-2-hydroxyglutaric aciduria http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=79315 OrphaNet: The portal for rare diseases and orphan drugs See also 2-hydroxyglutarate synthase 2-hydroxyglutarate dehydrogenase Hydroxyacid-oxoacid transhydrogenase Alpha-Hydroxyglutaric acid References External links 34515 600721 236792 none613657 none615182 none C535306 698870008 19 10761 2-hydroxyglutaric-aciduria Category:Inborn errors of metabolism Category:Autosomal recessive disorders Category:Rare diseases