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2-hydroxyglutarate aciduria

MedGen UID:
1689600
•Concept ID:
C5139239
•
Finding
HPO: HP:0032278

Definition

The concentration of 2-hydroxyglutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. [from HPO]

Professional guidelines

PubMed

An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study.
Steenweg ME, Jakobs C, Errami A, van Dooren SJ, Adeva Bartolomé MT, Aerssens P, Augoustides-Savvapoulou P, Baric I, Baumann M, Bonafé L, Chabrol B, Clarke JT, Clayton P, Coker M, Cooper S, Falik-Zaccai T, Gorman M, Hahn A, Hasanoglu A, King MD, de Klerk HB, Korman SH, Lee C, Meldgaard Lund A, Mejaski-Bosnjak V, Pascual-Castroviejo I, Raadhyaksha A, Rootwelt T, Roubertie A, Ruiz-Falco ML, Scalais E, Schimmel U, Seijo-Martinez M, Suri M, Sykut-Cegielska J, Trefz FK, Uziel G, Valayannopoulos V, Vianey-Saban C, Vlaho S, Vodopiutz J, Wajner M, Walter J, Walter-Derbort C, Yapici Z, Zafeiriou DI, Spreeuwenberg MD, Celli J, den Dunnen JT, van der Knaap MS, Salomons GS
Hum Mutat 2010 Apr;31(4):380-90. doi: 10.1002/humu.21197. PMID: 20052767
Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias.
Gibson KM, ten Brink HJ, Schor DS, Kok RM, Bootsma AH, Hoffmann GF, Jakobs C
Pediatr Res 1993 Sep;34(3):277-80. doi: 10.1203/00006450-199309000-00007. PMID: 8134166

Recent clinical studies

Etiology

Oxidative stress among L-2-hydroxyglutaric aciduria disease patients: evaluation of dynamic thiol/disulfide homeostasis.
Cansever MS, Zubarioglu T, Oruc C, Kiykim E, Gezdirici A, Neselioglu S, Erel O, Yalcinkaya C, Aktuglu-Zeybek C
Metab Brain Dis 2019 Feb;34(1):283-288. Epub 2018 Nov 29 doi: 10.1007/s11011-018-0354-8. PMID: 30499066
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.
Nota B, Struys EA, Pop A, Jansen EE, Fernandez Ojeda MR, Kanhai WA, Kranendijk M, van Dooren SJ, Bevova MR, Sistermans EA, Nieuwint AW, Barth M, Ben-Omran T, Hoffmann GF, de Lonlay P, McDonald MT, Meberg A, Muntau AC, Nuoffer JM, Parini R, Read MH, Renneberg A, Santer R, Strahleck T, van Schaftingen E, van der Knaap MS, Jakobs C, Salomons GS
Am J Hum Genet 2013 Apr 4;92(4):627-31. doi: 10.1016/j.ajhg.2013.03.009. PMID: 23561848Free PMC Article
L-2-hydroxyglutaric aciduria: a report of 29 patients.
Topçu M, Aydin OF, Yalçinkaya C, Haliloğlu G, Aysun S, Anlar B, Topaloğlu H, Turanli G, Yalnizoğlu D, Kesimer M, Coşkun T
Turk J Pediatr 2005 Jan-Mar;47(1):1-7. PMID: 15884621
D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders?
Korman SH, Salomons GS, Gutman A, Brooks R, Jakobs C
Neuropediatrics 2004 Jun;35(3):151-6. doi: 10.1055/s-2004-817905. PMID: 15248096
D-2-Hydroxyglutaric aciduria and subdural haemorrhage.
Kwong KL, Mak T, Fong CM, Poon KH, Wong SN, So KT
Acta Paediatr 2002;91(6):716-8. doi: 10.1080/080352502760069188. PMID: 12162609

Diagnosis

Separation and quantification of the urinary enantiomers of 2-hydroxyglutaric acid by capillary electrophoresis with capacitively coupled contactless conductivity detection: Application to the diagnosis of D- and L-2-hydroxyglutaric aciduria.
Cansever MŞ, Öztekin N, Kıykım E, Zübarioğlu T, Aktuğlu Zeybek AÇ
J Sep Sci 2023 Aug;46(16):e2300145. Epub 2023 Jun 3 doi: 10.1002/jssc.202300145. PMID: 37269210
Oncometabolites: A New Paradigm for Oncology, Metabolism, and the Clinical Laboratory.
Collins RRJ, Patel K, Putnam WC, Kapur P, Rakheja D
Clin Chem 2017 Dec;63(12):1812-1820. Epub 2017 Oct 16 doi: 10.1373/clinchem.2016.267666. PMID: 29038145
In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria.
Anghileri E, Bertolino N, Salsano E, Antelmi L, Carpinelli P, Castellotti B, Zucca I, Gellera C, Bisogno R, Caccia C, Cuccarini V
Brain Res 2016 Oct 1;1648(Pt A):506-511. Epub 2016 Aug 16 doi: 10.1016/j.brainres.2016.08.013. PMID: 27543339
D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic defect.
Struys EA
J Inherit Metab Dis 2006 Feb;29(1):21-9. doi: 10.1007/s10545-006-0317-9. PMID: 16601864
D-2-hydroxyglutaric aciduria.
Nyhan WL, Shelton GD, Jakobs C, Holmes B, Bowe C, Curry CJ, Vance C, Duran M, Sweetman L
J Child Neurol 1995 Mar;10(2):137-42. doi: 10.1177/088307389501000216. PMID: 7782605

Therapy

Enasidenib treatment in two individuals with D-2-hydroxyglutaric aciduria carrying a germline IDH2 mutation.
Geoerger B, Schiff M, Penard-Lacronique V, Darin N, Saad SM, Duchon C, Lamazière A, Desmons A, Pontoizeau C, Berlanga P, Ducassou S, Yen K, Su M, Schenkein D, Ottolenghi C, De Botton S
Nat Med 2023 Jun;29(6):1358-1363. Epub 2023 May 29 doi: 10.1038/s41591-023-02382-9. PMID: 37248298
IDH1 mutated acute myeloid leukemia in a child with metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria.
Srinivasan A, Zhou Y, Scordino T, Prabhu S, Wierenga A, Simon G, Wierenga KJ, Thompson J, Shah R, Sinha AA
Pediatr Hematol Oncol 2020 Aug;37(5):431-437. Epub 2020 Mar 13 doi: 10.1080/08880018.2020.1737284. PMID: 32166993
Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment.
Mühlhausen C, Salomons GS, Lukacs Z, Struys EA, van der Knaap MS, Ullrich K, Santer R
J Inherit Metab Dis 2014 Sep;37(5):775-81. Epub 2014 Apr 1 doi: 10.1007/s10545-014-9702-y. PMID: 24687295
L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings.
Seijo-Martínez M, Navarro C, Castro del Río M, Vila O, Puig M, Ribes A, Butron M
Arch Neurol 2005 Apr;62(4):666-70. doi: 10.1001/archneur.62.4.666. PMID: 15824270
Identification of the D-enantiomer of 2-hydroxyglutaric acid in glutaric aciduria type II.
Watanabe H, Yamaguchi S, Saiki K, Shimizu N, Fukao T, Kondo N, Orii T
Clin Chim Acta 1995 Jul 14;238(2):115-24. doi: 10.1016/0009-8981(95)06074-n. PMID: 7586571

Prognosis

Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment.
Mühlhausen C, Salomons GS, Lukacs Z, Struys EA, van der Knaap MS, Ullrich K, Santer R
J Inherit Metab Dis 2014 Sep;37(5):775-81. Epub 2014 Apr 1 doi: 10.1007/s10545-014-9702-y. PMID: 24687295
Isocitrate dehydrogenase 1/2 mutational analyses and 2-hydroxyglutarate measurements in Wilms tumors.
Rakheja D, Mitui M, Boriack RL, DeBerardinis RJ
Pediatr Blood Cancer 2011 Mar;56(3):379-83. Epub 2010 Nov 22 doi: 10.1002/pbc.22697. PMID: 21225914
L-2-hydroxyglutaric aciduria: a report of 29 patients.
Topçu M, Aydin OF, Yalçinkaya C, Haliloğlu G, Aysun S, Anlar B, Topaloğlu H, Turanli G, Yalnizoğlu D, Kesimer M, Coşkun T
Turk J Pediatr 2005 Jan-Mar;47(1):1-7. PMID: 15884621
L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings.
Seijo-Martínez M, Navarro C, Castro del Río M, Vila O, Puig M, Ribes A, Butron M
Arch Neurol 2005 Apr;62(4):666-70. doi: 10.1001/archneur.62.4.666. PMID: 15824270
D-2-Hydroxyglutaric aciduria and subdural haemorrhage.
Kwong KL, Mak T, Fong CM, Poon KH, Wong SN, So KT
Acta Paediatr 2002;91(6):716-8. doi: 10.1080/080352502760069188. PMID: 12162609

Clinical prediction guides

Enasidenib treatment in two individuals with D-2-hydroxyglutaric aciduria carrying a germline IDH2 mutation.
Geoerger B, Schiff M, Penard-Lacronique V, Darin N, Saad SM, Duchon C, Lamazière A, Desmons A, Pontoizeau C, Berlanga P, Ducassou S, Yen K, Su M, Schenkein D, Ottolenghi C, De Botton S
Nat Med 2023 Jun;29(6):1358-1363. Epub 2023 May 29 doi: 10.1038/s41591-023-02382-9. PMID: 37248298
Oxidative stress among L-2-hydroxyglutaric aciduria disease patients: evaluation of dynamic thiol/disulfide homeostasis.
Cansever MS, Zubarioglu T, Oruc C, Kiykim E, Gezdirici A, Neselioglu S, Erel O, Yalcinkaya C, Aktuglu-Zeybek C
Metab Brain Dis 2019 Feb;34(1):283-288. Epub 2018 Nov 29 doi: 10.1007/s11011-018-0354-8. PMID: 30499066
An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants.
Pop A, Williams M, Struys EA, Monné M, Jansen EEW, De Grassi A, Kanhai WA, Scarcia P, Ojeda MRF, Porcelli V, van Dooren SJM, Lennertz P, Nota B, Abdenur JE, Coman D, Das AM, El-Gharbawy A, Nuoffer JM, Polic B, Santer R, Weinhold N, Zuccarelli B, Palmieri F, Palmieri L, Salomons GS
J Inherit Metab Dis 2018 Mar;41(2):169-180. Epub 2017 Dec 13 doi: 10.1007/s10545-017-0106-7. PMID: 29238895Free PMC Article
In-vivo brain H1-MR-Spectroscopy identification and quantification of 2-hydroxyglutarate in L-2-Hydroxyglutaric aciduria.
Anghileri E, Bertolino N, Salsano E, Antelmi L, Carpinelli P, Castellotti B, Zucca I, Gellera C, Bisogno R, Caccia C, Cuccarini V
Brain Res 2016 Oct 1;1648(Pt A):506-511. Epub 2016 Aug 16 doi: 10.1016/j.brainres.2016.08.013. PMID: 27543339
Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment.
Mühlhausen C, Salomons GS, Lukacs Z, Struys EA, van der Knaap MS, Ullrich K, Santer R
J Inherit Metab Dis 2014 Sep;37(5):775-81. Epub 2014 Apr 1 doi: 10.1007/s10545-014-9702-y. PMID: 24687295

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