Cited by 292Metabolism and Genetic DisordersAmino Acid Enzymes and MetabolismNeurological diseases and metabolism

The DOI matches its Crossref record; 92 of the 93 references it cites were found in a registry or an index.

Progress in understanding 2‐hydroxyglutaric acidurias

Open access

Kranendijk, Martijn, Struys, Eduard A., Salomons, Gajja S., Van der Knaap, Marjo S., Jakobs, Cornelis·2012·Journal of Inherited Metabolic Disease

DOI 10.1007/s10545-012-9462-5PMC PMC3388262

Open this paper in CoChat — free account Open PDF

Abstract

The organic acidurias d‐2‐hydroxyglutaric aciduria (D‐2‐HGA), l‐2‐hydroxyglutaric aciduria (L‐2‐HGA), and combined d,l‐2‐hydroxyglutaric aciduria (D,L‐2‐HGA) cause neurological impairment at young age. Accumulation of d‐2‐hydroxyglutarate (D‐2‐HG) and/or l‐2‐hydroxyglutarate (L‐2‐HG) in body fluids are the biochemical hallmarks of these disorders. The current review describes the knowledge gathered on 2‐hydroxyglutaric acidurias (2‐HGA), since the description of the first patients in 1980. We report on the clinical, genetic, enzymatic and metabolic characterization of D‐2‐HGA type I, D‐2‐HGA type II, L‐2‐HGA and D,L‐2‐HGA, whereas for D‐2‐HGA type I and type II novel clinical information is presented which was derived from questionnaires.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s10545-012-9462-5

Cites

92 of 92 references verified0 citation errors · 0 not checkable

Statistics

Fig. 1 2-hydroxyglutaric acid with a chiral center at the 2nd carbon (*)CC BY · PubMed Central

Fig. 2 Enantiomers d- and l-2-hydroxyglutaric acid (D-2-HG and L-2-HG, systemic IUPAC names included)CC BY · PubMed Central

Fig. 3 Enzymes L-malDH and HOT are responsible for production of D-2-HG and L-2-HG from 2-KGCC BY · PubMed Central

Fig. 4 Mutations reported in D2HGDH (Misra et al 2005; Struys et al 2005a, b; Haliloglu et al 2009; Kranendijk et al 2010a; Pervaiz et al 2011)CC BY · PubMed Central

Fig. 5 D-2-HG is formed from 2-KG via HOT. D-2-HGDH catalyzes the conversion of D-2-HG to 2-KG. D-2-HG accumulates in D-2-HGA type I patients when D-2-HGDH is impairedCC BY · PubMed Central

Fig. 6 Novel IDH2-mutant gain-of-function produces D-2-HG from 2-KG in addition to production of D-2-HG via HOT. It is hypothesized that D-2-HGDH cannot fully metabolize all of the generated D-2-HG, resulting in D-2-HG accumulation in D-2-HGA type IICC BY · PubMed Central

Fig. 7 L-2-HG is formed via the non-specific interaction of L-malDH with 2-KG using NADH. The “enzyme of metabolite repair” L-2-HGDH catalyzes the interconversion of L-2-HG to 2-KG using FAD as cofactor. L-2-HG accumulates in L-2-HGA patients when L-2-HGDH is impairedCC BY · PubMed Central

Fig. 8 Diagnostic flow chart for 2-hydroxyglutaric aciduriasCC BY · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020
Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α
Zhao, S., Lin, Y., Xu, W., Jiang, W., Zha, Z., Wang, P., Yu, W., Li, Z., Gong, L., Peng, Y., et al. (2009) · Science · doi:10.1126/science.1170944 · Cited by 1,119
Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations
Gross, S., Cairns, R. A., Minden, M. D., Driggers, E. M., Bittinger, M. A., Jang, H. G., Sasaki, M., Jin, S., Schenkein, D. P., Su, S. M., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20092506 · Cited by 736
ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency
Olsen, R. K. J., Olpin, S. E., Andresen, B. S., Miedzybrodzka, Z., Pourfarzam, M., Merinero, B., Frerman, F. E., Beresford, M. W., Dean, J., Cornelius, N., et al. (2007) · Brain · doi:10.1093/brain/awm135 · Cited by 319
L‐2‐Hydroxyglutaric aciduria: an inborn error of metabolism?
Duran, M., Kamerling, J. P., Bakker, H. D., van Gennip, A. H., & Wadman, S. K. (1980) · Journal of Inherited Metabolic Disease · doi:10.1007/bf02312543 · Cited by 226
Inherited disorders of GABA metabolism
Jakobs, C., Jaeken, J., & Gibson, K. M. (1993) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711902 · Cited by 225
Self-citation
IDH2 Mutations in Patients with d -2-Hydroxyglutaric Aciduria
Kranendijk, M., Struys, E. A., van Schaftingen, E., Gibson, K. M., Kanhai, W. A., van der Knaap, M. S., Amiel, J., Buist, N. R., Das, A. M., de Klerk, J. B., et al. (2010) · Science · doi:10.1126/science.1192632 · Cited by 195
Self-citation

Show all 93 references

Sorted by citations

Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021
IDH1 and IDH2 mutations in gliomas
Cohen, A. L., Holmen, S. L., & Colman, H. (2013) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-013-0345-4 · Cited by 629
What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer
Losman, J.-A., & Kaelin, W. G. (2013) · Genes & Development · doi:10.1101/gad.217406.113 · Cited by 570
Hypoxia Induces Production of L-2-Hydroxyglutarate
Intlekofer, A. M., Dematteo, R. G., Venneti, S., Finley, L. W. S., Lu, C., Judkins, A. R., Rustenburg, A. S., Grinaway, P. B., Chodera, J. D., Cross, J. R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.023 · Cited by 513
IDH mutations in cancer and progress toward development of targeted therapeutics
Dang, L., Yen, K., & Attar, E. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw013 · Cited by 509
IDH1andIDH2Mutations in Tumorigenesis: Mechanistic Insights and Clinical Perspectives
Yang, H., Ye, D., Guan, K., & Xiong, Y. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1773 · Cited by 477
Oncometabolites: linking altered metabolism with cancer
Yang, M. H., Soga, T., & Pollard, P. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67228 · Cited by 441
Coupling Krebs cycle metabolites to signalling in immunity and cancer
Ryan, D. G., Murphy, M. P., Frezza, C., Prag, H. A., Chouchani, E. T., O’Neill, L. A., & Mills, E. L. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0014-7 · Cited by 398
The metabolite α-KG induces GSDMC-dependent pyroptosis through death receptor 6-activated caspase-8
Zhang, J.-Y., Zhou, B., Sun, R.-Y., Ai, Y.-L., Cheng, K., Li, F.-N., Wang, B.-R., Liu, F.-J., Jiang, Z., Wang, W., et al. (2021) · Cell Research · doi:10.1038/s41422-021-00506-9 · Cited by 394
Hypoxia-Mediated Increases in l -2-hydroxyglutarate Coordinate the Metabolic Response to Reductive Stress
Oldham, W. M., Clish, C. B., Yang, Y., & Loscalzo, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.021 · Cited by 364
“Two enantiomers of 2HG, L and D, have been associated with separate, rare inborn errors of metabolism resulting in increased urinary excretion of 2HG linked to neurological deficits in children (Chalmers et al., 1980; Duran et al., 1980; Kranendijk et al., 2012).”
Metabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322
Metabolite damage and its repair or pre-emption
Linster, C. L., SCHAFTINGEN, E. V., & Hanson, A. D. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1141 · Cited by 273
Detection and analysis of chiral molecules as disease biomarkers
Liu, Y., Wu, Z., Armstrong, D. W., Wolosker, H., & Zheng, Y. (2023) · Nature Reviews Chemistry · doi:10.1038/s41570-023-00476-z · Cited by 261
Metabolism, Activity, and Targeting of D- and L-2-Hydroxyglutarates
Ye, D., Guan, K.-L., & Xiong, Y. (2018) · Trends in Cancer · doi:10.1016/j.trecan.2017.12.005 · Cited by 242
2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling
Fu, X., Chin, R., Vergnes, L., Hwang, H., Deng, G., Xing, Y., Pai, M. Y., Li, S., Ta, L. H., Fazlollahi, F., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.009 · Cited by 230
Hypoxia/pseudohypoxia‐mediated activation of hypoxia‐inducible factor‐1α in cancer
Hayashi, Y., Yokota, A., Harada, H., & Huang, G. (2019) · Cancer Science · doi:10.1111/cas.13990 · Cited by 229
IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives
de Botton, S., Mondesir, J., Willekens, C., & Touat, M. (2016) · Journal of Blood Medicine · doi:10.2147/jbm.s70716 · Cited by 220
Applications of NMR spectroscopy to systems biochemistry
Fan, T. W. ‐., & Lane, A. N. (2016) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2016.01.005 · Cited by 220
Isocitrate Dehydrogenase Mutation and ( R )-2-Hydroxyglutarate: From Basic Discovery to Therapeutics Development
Dang, L., & Su, S.-S. M. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044732 · Cited by 204
The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation
Molenaar, R. J., Radivoyevitch, T., Maciejewski, J. P., Noorden, C. J. F. V., & Bleeker, F. E. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.05.004 · Cited by 186
Oncometabolites: Unconventional triggers of oncogenic signalling cascades
Sciacovelli, M., & Frezza, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.025 · Cited by 184
Cancer-associated mutation and beyond: The emerging biology of isocitrate dehydrogenases in human disease
Tommasini-Ghelfi, S., Murnan, K., Kouri, F. M., Mahajan, A., May, J., & Stegh, A. H. (2019) · Science Advances · doi:10.1126/sciadv.aaw4543 · Cited by 166
The Roles of 2-Hydroxyglutarate
Du, X., & Hu, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.651317 · Cited by 160
Radioprotection of IDH1 -Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198
Molenaar, R. J., Botman, D., Smits, M. A., Hira, V. V., van Lith, S. A., Stap, J., Henneman, P., Khurshed, M., Lenting, K., Mul, A. N., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3603 · Cited by 148
Deficiency in SLC25A1, Encoding the Mitochondrial Citrate Carrier, Causes Combined D-2- and L-2-Hydroxyglutaric Aciduria
Nota, B., Struys, E. A., Pop, A., Jansen, E. E., Fernandez Ojeda, M. R., Kanhai, W. A., Kranendijk, M., van Dooren, S. J. M., Bevova, M. R., Sistermans, E. A., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.03.009 · Cited by 138
Self-citation
2-Hydroxyglutarate in Cancer Cells
Ježek, P. (2020) · Antioxidants & Redox Signaling · doi:10.1089/ars.2019.7902 · Cited by 130
Isocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight
Al‐Khallaf, H. (2017) · Cell & Bioscience · doi:10.1186/s13578-017-0165-3 · Cited by 133
Cardio-onco-metabolism: metabolic remodelling in cardiovascular disease and cancer
Karlstaedt, A., Moslehi, J. J., & de Boer, R. A. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00698-6 · Cited by 130
Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response
Fathi, A. T., Sadrzadeh, H., Borger, D. R., Ballen, K. K., Amrein, P. C., Attar, E. C., Foster, J., Burke, M. E., Lopez, H. U., Matulis, C. R., et al. (2012) · Blood · doi:10.1182/blood-2012-06-438267 · Cited by 125
Functional Assessment of Lipoyltransferase-1 Deficiency in Cells, Mice, and Humans
Ni, M., Solmonson, A., Pan, C., Yang, C., Li, D., Notzon, A., Cai, L., Guevara, G., Zacharias, L. G., Faubert, B., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.005 · Cited by 124
Isocitrate Dehydrogenase (IDH) Mutations Promote a Reversible ZEB1/MicroRNA (miR)-200-dependent Epithelial-Mesenchymal Transition (EMT)
Grassian, A. R., Lin, F., Barrett, R., Liu, Y., Jiang, W., Korpal, M., Astley, H. M., Gitterman, D. P., Henley, T., Howes, R., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.417832 · Cited by 122
Diseases Caused by Mutations in Mitochondrial Carrier Genes SLC25: A Review
Palmieri, F., Scarcia, P., & Monné, M. (2020) · Biomolecules · doi:10.3390/biom10040655 · Cited by 124
Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells
Li, L., Paz, A. C., Wilky, B. A., Johnson, B. A., Galoian, K. A., Rosenberg, A. E., Hu, G., Tinoco, G., Bodamer, O. A., & Trent, J. C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133813 · Cited by 107
Metabolic dysregulation in monogenic disorders and cancer — finding method in madness
Erez, A., & DeBerardinis, R. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3949 · Cited by 105
New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma
Dimitrov, L., Hong, C. S., Yang, C., Zhuang, Z., & Heiss, J. D. (2015) · International Journal of Medical Sciences · doi:10.7150/ijms.11047 · Cited by 108
Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1
Rajendran, V. (2016) · Molecular BioSystems · doi:10.1039/c6mb00182c · Cited by 98
Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate
Knorr, S., Sinn, M., Galetskiy, D., Williams, R. M., Wang, C., Müller, N., Mayans, O. M., Schleheck, D., & Hartig, J. S. (2018) · Nature Communications · doi:10.1038/s41467-018-07563-6 · Cited by 97
The multifaceted contribution of α-ketoglutarate to tumor progression: An opportunity to exploit?
Abla, H., Sollazzo, M., Gasparre, G., Iommarini, L., & Porcelli, A. M. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.031 · Cited by 99
Oncometabolites: A New Paradigm for Oncology, Metabolism, and the Clinical Laboratory
Collins, R. R. J., Patel, K., Putnam, W. C., Kapur, P., & Rakheja, D. (2017) · Clinical Chemistry · doi:10.1373/clinchem.2016.267666 · Cited by 94
D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in micePreprint
Akbay, E. A., Moslehi, J. J., Christensen, C. L., Saha, S. K., Tchaicha, J. H., Ramkissoon, S. H., Stewart, K. M., Carretero, J., Kikuchi, E., Zhang, H., et al. (2014) · Genes & Development · doi:10.1101/gad.231233.113 · Cited by 93
Genetically-defined metabolic reprogramming in cancer
Mullen, A. R., & DeBerardinis, R. J. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.06.009 · Cited by 90
D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2
Lin, A., Abbas, S., Kim, S., Ortega, M. M., Bouamar, H., Escobedo, Y. A., Varadarajan, P., Qin, Y., Sudderth, J., Schulz, E., et al. (2015) · Nature Communications · doi:10.1038/ncomms8768 · Cited by 88
Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases
Tarhonskaya, H., Rydzik, A. M., Leung, I. K. H., Loik, N. D., Chan, M. C., Kawamura, A., McCullagh, J. S. O., Claridge, T. D. W., Flashman, E., & Schofield, C. J. (2014) · Nature Communications · doi:10.1038/ncomms4423 · Cited by 80
Neurological manifestations of organic acidurias
Wajner, M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0161-9 · Cited by 79
Mutations in the Isocitrate Dehydrogenase Genes IDH1 and IDH2 in Tumors
Schaap, F. G., French, P. J., & Bovée, J. V. M. G. (2012) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e31827b654d · Cited by 80
The Mitochondrial Citrate Carrier SLC25A1/CIC and the Fundamental Role of Citrate in Cancer, Inflammation and Beyond
Mosaoa, R., Kasprzyk-Pawelec, A., Fernandez, H. R., & Avantaggiati, M. L. (2021) · Biomolecules · doi:10.3390/biom11020141 · Cited by 80
Saccharomyces cerevisiae Forms d-2-Hydroxyglutarate and Couples Its Degradation to d-Lactate Formation via a Cytosolic Transhydrogenase
Becker‐Kettern, J., Paczia, N., Conrotte, J., Kay, D. P., Guignard, C., Jung, P. P., & Linster, C. L. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.704494 · Cited by 76
Metabolite proofreading, a neglected aspect of intermediary metabolism
SCHAFTINGEN, E. V., Rim, R., Marbaix, A., Collard, F., Veiga‐da‐Cunha, M., & Linster, C. L. (2013) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-012-9571-1 · Cited by 67
Cancer-associated 2-oxoglutarate analogues modify histone methylation by inhibiting histone lysine demethylases
Laukka, T., Myllykoski, M., Looper, R., & Koivunen, P. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.06.048 · Cited by 69
Current concepts in organic acidurias: understanding intra‐ and extracerebral disease manifestation
Kölker, S., Burgard, P., Sauer, S. W., & Okun, J. G. (2013) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-013-9600-8 · Cited by 62
IDH Mutations in Tumorigenesis and Their Potential Role As Novel Therapeutic Targets
Krell, D., Mulholland, P. J., Frampton, A. E., Krell, J., Stebbing, J., & Bardella, C. (2013) · Future Oncology · doi:10.2217/fon.13.143 · Cited by 63
Diagnostic Value of Plasma and Urinary 2-Hydroxyglutarate to Identify Patients With Isocitrate Dehydrogenase-Mutated Glioma
Lombardi, G., Corona, G., Bellu, L., Puppa, A. D., Pambuku, A., Fiduccia, P., Bertorelle, R., Gardiman, M. P., D’Avella, D., Toffoli, G., et al. (2015) · The Oncologist · doi:10.1634/theoncologist.2014-0266 · Cited by 61
Diagnostic Approach to Macrocephaly in Children
Accogli, A., Geraldo, A. F., Piccolo, G., Riva, A., Scala, M., Balagura, G., Salpietro, V., Madia, F., Maghnie, M., Zara, F., et al. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2021.794069 · Cited by 60
Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations
Hvinden, I. C., Cadoux-Hudson, T. A. D., Schofield, C. J., & McCullagh, J. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100469 · Cited by 63
From genomics to the clinic: biological and translational insights of mutant IDH1/2 in glioma
Dunn, G. P., Andronesi, O. C., & Cahill, D. P. (2013) · Neurosurgical FOCUS · doi:10.3171/2012.12.focus12355 · Cited by 59
A Mouse Model of L-2-Hydroxyglutaric Aciduria, a Disorder of Metabolite Repair
Rim, R., Achouri, Y., Marbaix, É., Schakman, O., Wiame, E., Marie, S., Gailly, P. L., Vincent, M., Veiga‐da‐Cunha, M., & SCHAFTINGEN, E. V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119540 · Cited by 60
Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy
Chung, W. K., Martin, K., Jalas, C., Braddock, S. R., Juusola, J., Monaghan, K. G., Warner, B. B., Franks, S., Yudkoff, M., Lulis, L., et al. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103140 · Cited by 58
Metabolism navigates neural cell fate in development, aging and neurodegeneration
Traxler, L., Lagerwall, J., Eichhorner, S., Stefanoni, D., D’Alessandro, A., & Mertens, J. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.048993 · Cited by 59
D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth
Ma, S., Jiang, B., Deng, W., Gu, Z.-K., Wu, F.-Z., Li, T., Xia, Y., Yang, H., Ye, D., Xiong, Y., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3330 · Cited by 57
The clinical use of IDH1 and IDH2 mutations in gliomas
Pïcca, A., Berzero, G., Stefano, A. L. D., & Sanson, M. (2018) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2018.1548935 · Cited by 55
Hypoxia and GABA shunt activation in the pathogenesis of Alzheimer's disease
Salminen, A., Jouhten, P., Sarajärvi, T., Haapasalo, A., & Hiltunen, M. O. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.11.005 · Cited by 56
Endogenous toxic metabolites and implications in cancer therapy
Lee, N., Spears, M. E., Carlisle, A. E., & Kim, D. (2020) · Oncogene · doi:10.1038/s41388-020-01395-9 · Cited by 56
Metabolism-driven chromatin dynamics: Molecular principles and technological advances
Sahu, V., & Lü, C. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.12.012 · Cited by 56
Organic acidurias: Major gaps, new challenges, and a yet unfulfilled promise
Dimitrov, B., Molema, F., Williams, M., Schmiesing, J., Mühlhausen, C., Baumgartner, M. R., Schumann, A., & Kölker, S. (2020) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12254 · Cited by 51
Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate
Hunt, R. J., Granat, L., McElroy, G. S., Ranganathan, R., Chandel, N. S., & Bateman, J. M. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201904148 · Cited by 49
Enantiomer-specific and paracrine leukemogenicity of mutant IDH metabolite 2-hydroxyglutarate
Chaturvedi, A., Cruz, M. M. A., Jyotsana, N., Sharma, A., Goparaju, R., Schwarzer, A., Görlich, K., Schottmann, R., Struys, E. A., Jansen, E. E. W., et al. (2016) · Leukemia · doi:10.1038/leu.2016.71 · Cited by 50
Self-citation
Enantioselective metabolomics by liquid chromatography-mass spectrometry
Calderón, C., & Lämmerhofer, M. (2021) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2021.114430 · Cited by 48
D2HGDH-mediated D2HG catabolism enhances the anti-tumor activities of CAR-T cells in an immunosuppressive microenvironment
Yang, Q., Hao, J., Chi, M., Wang, Y., Li, J., Huang, J., Zhang, J., Zhang, M., Lu, J., Zhou, S., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.007 · Cited by 47
A feedback loop engaging propionate catabolism intermediates controls mitochondrial morphology
Zhou, J., Duan, M., Wang, X., Zhang, F., Zhou, H., Ma, T., Yin, Q., Zhang, J., Tian, F., Wang, G., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00883-2 · Cited by 47
Cardiac Complications of Propionic and Other Inherited Organic Acidemias
Park, K. C., Krywawych, S., Richard, E., Desviat, L. R., & Swietach, P. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.617451 · Cited by 48
Cardio-Oncology
Karlstaedt, A., Barrett, M., Hu, R., Gammon, S. T., & Ky, B. (2021) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2021.05.008 · Cited by 48
Coupling between d -3-phosphoglycerate dehydrogenase and d -2-hydroxyglutarate dehydrogenase drives bacterial l -serine synthesis
Zhang, W., Zhang, M., Gao, C., Zhang, Y., Ge, Y., Guo, S., Guo, X., Zhou, Z., Liu, Q., Zhang, Y., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619034114 · Cited by 47
IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy
Neal, A. J., Kwan, P., O'Brien, T. J., Buckland, M. E., Gonzales, M. F., & Morokoff, A. P. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.10.027 · Cited by 46
The oncometabolite D-2-hydroxyglutarate induced by mutant IDH1 or -2 blocks osteoblast differentiation in vitro and in vivo
Suijker, J., Baelde, H. J., Roelofs, H., Cleton-Jansen, A., & Bovée, J. V. M. G. (2015) · Oncotarget · doi:10.18632/oncotarget.4024 · Cited by 47
To be Wild or Mutant: Role of Isocitrate Dehydrogenase 1 (IDH1) and 2-Hydroxy Glutarate (2-HG) in Gliomagenesis and Treatment Outcome in Glioma
Bhavya, B., Reghuvaran, A. C., Madhusoodanan, U. K., Rajalakshmi, P., Krishnakumar, K., Easwer, H. V., Deepti, A. N., & Gopala, S. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00730-3 · Cited by 46
d-2-Hydroxyglutarate is an anti-inflammatory immunometabolite that accumulates in macrophages after TLR4 activation
de Goede, K. E., Harber, K. J., Gorki, F. S., Verberk, S. G. S., Groh, L. A., Keuning, E. D., Struys, E. A., van Weeghel, M., Haschemi, A., de Winther, M. P. J., et al. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166427 · Cited by 43
Self-citation
Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression
Pirozzi, C. J., Carpenter, A. B., Waitkus, M. S., Wang, C. Y., Zhu, H., Hansen, L. J., Chen, L. H., Greer, P. K., Feng, J., Wang, Y., et al. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0485 · Cited by 42
Metabolite Proofreading in Carnosine and Homocarnosine Synthesis
Veiga‐da‐Cunha, M., Chevalier, N., Stroobant, V., Vertommen, D., & SCHAFTINGEN, E. V. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.576579 · Cited by 41
Mitochondrial 2-hydroxyglutarate metabolism
Engqvist, M. K. M., Eßer, C., Maier, A., Lercher, M. J., & Maurino, V. G. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.02.009 · Cited by 46
Metabolic Regulation of Hypoxia-Inducible Transcription Factors: The Role of Small Molecule Metabolites and Iron
Bailey, P. S. J., & Nathan, J. A. (2018) · Biomedicines · doi:10.3390/biomedicines6020060 · Cited by 41
An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR
Kang, Z., Zhang, M., Gao, K., Zhang, W., Meng, W., Liu, Y., Xiao, D., Guo, S., Ma, C., Gao, C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23723-7 · Cited by 41
Combined D2‐/L2‐hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course and effects of citrate treatment
Mühlhausen, C., Salomons, G. S., Lukács, Z., Struys, E. A., van der Knaap, M. S., Ullrich, K., & Santer, R. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9702-y · Cited by 40
Self-citation
Malic enzyme 2 maintains protein stability of mutant p53 through 2-hydroxyglutarate
Zhao, M., Yao, P., Mao, Y., Wu, J., Wang, W., Geng, C., Cheng, J., Du, W., & Jiang, P. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00532-w · Cited by 40
Quantitation of isocitrate dehydrogenase (IDH)-induced D and L enantiomers of 2-hydroxyglutaric acid in biological fluids by a fully validated liquid tandem mass spectrometry method, suitable for clinical applications
Poinsignon, V., Mercier, L., Nakabayashi, K., David, M. D., Lalli, A., Penard‐Lacronique, V., Quivoron, C., Saada, V., de Botton, S., Broutin, S., et al. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.04.030 · Cited by 43
Lactate Dehydrogenase C Produces S-2-Hydroxyglutarate in Mouse Testis
Teng, X., Emmett, M. J., Lazar, M. A., Goldberg, E., & Rabinowitz, J. D. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00290 · Cited by 39
L2hgdh Deficiency Accumulates l -2-Hydroxyglutarate with Progressive Leukoencephalopathy and Neurodegeneration
Ma, S., Sun, R., Jiang, B., Gao, J., Deng, W., Liu, P., He, R., Cui, J., Ji, M., Yi, W., et al. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00492-16 · Cited by 39
Metabolic Drivers in Hereditary Cancer Syndromes
Sciacovelli, M., Schmidt, C., Maher, E. R., & Frezza, C. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033612 · Cited by 39
Inborn errors of metabolism leading to neuronal migration defects
Schiller, S. A., Rosewich, H., Grünewald, S., & Gärtner, J. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12194 · Cited by 38
Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin
Biedermann, J., Preussler, M., Conde, M., Peitzsch, M., Richter, S., Wiedemuth, R., Abou‐El‐Ardat, K., Krüger, A., Meinhardt, M., Schackert, G., et al. (2019) · Cancers · doi:10.3390/cancers11122028 · Cited by 36
Imaging Manifestations of the Leukodystrophies, Inherited Disorders of White Matter
Yang, E., & Prabhu, S. P. (2014) · Radiologic Clinics of North America · doi:10.1016/j.rcl.2013.11.008 · Cited by 35
L-2-Hydroxyglutarate Protects Against Cardiac Injury via Metabolic Remodeling
He, H., Mulhern, R. M., Oldham, W. M., Xiao, W., Lin, Y., Liao, R., & Loscalzo, J. (2022) · Circulation Research · doi:10.1161/circresaha.122.321227 · Cited by 35
Inborn errors of metabolite repair
Veiga‐da‐Cunha, M., SCHAFTINGEN, E. V., & Bommer, G. T. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12187 · Cited by 34
A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR
Xiao, D., Zhang, W., Guo, X., Liu, Y., Hu, C., Guo, S., Kang, Z., Xu, X., Ma, C., Gao, C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27357-7 · Cited by 34
Chiral separation of 2-hydroxyglutaric acid on cinchonan carbamate based weak chiral anion exchangers by high-performance liquid chromatography
Calderón, C., Horak, J., & Lämmerhofer, M. (2016) · Journal of Chromatography A · doi:10.1016/j.chroma.2016.05.042 · Cited by 32
Experimental evidence of oxidative stress in patients with l-2-hydroxyglutaric aciduria and that l-carnitine attenuates in vitro DNA damage caused by d-2-hydroxyglutaric and l-2-hydroxyglutaric acids
Rodrigues, D. G. B., Coelho, D. D. M., Sitta, Â., Jacques, C. E. D., Hauschild, T. C., Manfredini, V., Bakkali, A., Struys, E. A., Jakobs, C., Wajner, M., et al. (2017) · Toxicology in Vitro · doi:10.1016/j.tiv.2017.04.006 · Cited by 32
Self-citation
MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome
Qiu, Z., Lin, A., Jiang, S., Elkashef, S. M., Myers, J., Srikantan, S., Sasi, B. K., Cao, J. Z., Godley, L. A., Rakheja, D., et al. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.02.002 · Cited by 31
In vivo intracerebral administration of L-2-hydroxyglutaric acid provokes oxidative stress and histopathological alterations in striatum and cerebellum of adolescent rats
da Rosa, M. S., Ribeiro, C. A. J., Seminotti, B., Ribeiro, R. T., Amaral, A. U., Coelho, D. D. M., de Oliveira, F. H., Leipnitz, G., & Wajner, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.02.008 · Cited by 33
Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria
Prasun, P., Young, S. P., Salomons, G. S., Werneke, A. M., Jiang, Y., Struys, E. A., Paige, M. A., Avantaggiati, M. L., & McDonald, M. (2014) · JIMD Reports · doi:10.1007/8904_2014_378 · Cited by 30
Self-citation
Successive distinct high‐grade gliomas in L‐2‐hydroxyglutaric aciduria
Patay, Z. J., Orr, B. A., Shulkin, B. L., Hwang, S. N., Yuan, Y., Broniscer, A., Boop, F. A., & Ellison, D. W. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9782-8 · Cited by 29
Epigenetic Modifiers in Normal and Malignant Hematopoiesis
Haladyna, J. N., Yamauchi, T., Neff, T., & Bernt, K. M. (2015) · Epigenomics · doi:10.2217/epi.14.88 · Cited by 30

Authors: Kranendijk, M., Struys, E. A., Salomons, G. S., Van der Knaap, M. S., & Jakobs, C.
Affiliations: Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Paediatric Neurology VU University Medical Center Amsterdam The Netherlands
Corresponding author: Jakobs, Cornelis
ORCID: Struys, Eduard A.
Salomons, Gajja S.
Jakobs, Cornelis
Venue: Journal of Inherited Metabolic Disease
Publisher: Wiley
Published: 2012-03-06
Volume: 35
Issue: 4
Pages: 571-587
ISSN: 0141-8955 (ISSN-L)
1573-2665
DOI: 10.1007/s10545-012-9462-5
PMC: PMC3388262
OpenAlex: W2058747828
Cited by: 292
References: 93
Citations by year: 2026: 11 · 2025: 14 · 2024: 33 · 2023: 20 · 2022: 29 · 2021: 23 · 2020: 20 · 2019: 22 · 2018: 16 · 2017: 14 · 2016: 22 · 2015: 27 · 2014: 15 · 2013: 15 · 2012: 10
FWCI: 2.56
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Journal of Inherited Metabolic Disease (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
VU Research Portal (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords: L-2-hydroxyglutaric aciduria, D-2-hydroxyglutarate, L-2-hydroxyglutarate, organic aciduria, neurological deficit, genetic characterization, enzyme characterization, metabolic characterization, clinical features, patient survey
MeSH terms: Humans, Nervous System Diseases, Brain Diseases, Metabolic, Inborn

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Progress in understanding 2‐hydroxyglutaric acidurias

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks