An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype–phenotype study†
Marjan E. Steenweg
Department of Child Neurology and VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorCornelis Jakobs
Metabolic Unit of the Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorSilvy J.M. van Dooren
Metabolic Unit of the Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorMaria T. Adeva Bartolomé
Hospital Virgen del Puerto, Plasencia, Céceres, Spain
Search for more papers by this authorPeter Aerssens
Department of Pediatrics, Virga Jesse Hospital, Hasselt, Belgium
Search for more papers by this authorPersephone Augoustides-Savvapoulou
Department of Pediatrics-Metabolic Lab., Aristotle University of Thessaloniki, Hippocration General Hospital, Thessaloniki, Greece
Search for more papers by this authorIvo Baric
Department of Pediatrics, University Hospital Center, Zagreb, Croatia
Search for more papers by this authorMatthias Baumann
Department of Pediatrics, Division of Pediatric Neurology and Inherited Metabolic Disorders, Medical University of Innsbruck, Austria
Search for more papers by this authorLuisa Bonafé
Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanna, Switzerland
Search for more papers by this authorBrigitte Chabrol
Department of Metabolic Disease, Hospital Timone Enfants, Marseille, France
Search for more papers by this authorJoe T.R. Clarke
Division of Clinical & Metabolic Genetics, Hospital for Sick Children, Toronto, Canada
Search for more papers by this authorPeter Clayton
Department of Paediatric Metabolic Disease and Hepatology, Institute of Child Health, University College London, Great Ormond Street Hospital for Children, London, United Kingdom
Search for more papers by this authorMahmut Coker
Department of Pediatrics, Ege University Medical Faculty, Bornova, Izmir, Turkey
Search for more papers by this authorSarah Cooper
Department of Neurology, Southern General Hospital, Glasgow, United Kingdom
Search for more papers by this authorTzipora Falik-Zaccai
Institute of Human Genetics, Western Galilee Hospital, Naharia, Rappaport Faculty of Medicine, Haifa, Israel
Search for more papers by this authorMark Gorman
Department of Neurology, Children's Hospital Boston, Boston, Massachusetts
Search for more papers by this authorAndreas Hahn
Department of Pediatric Neurology, Giessen, Germany
Search for more papers by this authorAlev Hasanoglu
Department of Pediatric Metabolism and Nutrition, At Gazi University Faculty of Medicine, Turkey
Search for more papers by this authorMary D. King
Department of Pediatric Neurology, Children's University Hospital, Dublin, Ireland
Search for more papers by this authorHans B.C. de Klerk
Department of Pediatrics, Erasmus mc/Sophia Childrens Hospital Rotterdam, Rotterdam, The Netherlands
Search for more papers by this authorStanley H. Korman
Metabolic Disease Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Search for more papers by this authorCéline Lee
Children's Hospital, University of Bonn, Bonn, Germany
Search for more papers by this authorAllan Meldgaard Lund
Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark
Search for more papers by this authorVlatka Mejaški-Bošnjak
Department of Child Neurology, Children's Hospital Zagreb, Zagreb, Croatia
Search for more papers by this authorIgnacio Pascual-Castroviejo
Department of Pediatric Neurology, Hospital “La Paz,” Madrid, Spain
Search for more papers by this authorAparna Raadhyaksha
Medical Genetics, University of Miami, Florida
Search for more papers by this authorTerje Rootwelt
Division of Pediatrics, Rikshospitalet, Oslo University Hospital, Norway
Search for more papers by this authorAgathe Roubertie
CHU Montpellier, Department of Pediatric Neurology, Hospital Gui de Chauliac, Montpellier, France
Search for more papers by this authorMaria L. Ruiz-Falco
Department of Pediatric Neurology, Hospital Niño Jesús, Madrid, Spain
Search for more papers by this authorEmmanuel Scalais
Department of Pediatrics, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
Search for more papers by this authorManuel Seijo-Martinez
Department of Neurology, Hospital do Salnes, Villagarcia, Spain
Search for more papers by this authorMohnish Suri
Nottingham City Hospital, Clinical Genetics, Nottingham, United Kingdom
Search for more papers by this authorJolanta Sykut-Cegielska
Department of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland
Search for more papers by this authorFriedrich K. Trefz
Department of Pediatrics, Klinikum am Steinenberg, Reutlingen, Germany
Search for more papers by this authorGraziella Uziel
Child Neurology Department, National Institute for Neurology “Carlo Besta,” Milan, Italy
Search for more papers by this authorVassili Valayannopoulos
Department of Neuro-Metabolism, Hospital Necker Des Enfants Malades, Paris, France
Search for more papers by this authorChristine Vianey-Saban
Centre de Biotechnology Cellulaire, Hopital Debrousse, Lyon, France
Search for more papers by this authorStefan Vlaho
Department of Pediatric Neurology, Klinik für Kinder-und Jugendmedizin, Johann Wolfgang Goethe-University, Frankfurt, Germany
Search for more papers by this authorJulia Vodopiutz
Department for Inborn Errors of Metabolism and Pediatric Genetics, University Children's Hospital Vienna, Vienna, Austria
Search for more papers by this authorMoacir Wajner
Department of Medical Genetics, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brasil
Search for more papers by this authorJohn Walter
Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom
Search for more papers by this authorClaudia Walter-Derbort
Department of Pediatrics, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany
Search for more papers by this authorZuhal Yapici
Department of Neurology, Istanbul University, Faculty of Medicine, Istanbul, Turkey
Search for more papers by this authorDimitrios I. Zafeiriou
Department of Child Neurology and Developmental Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece
Search for more papers by this authorMarieke D. Spreeuwenberg
Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorJacopo Celli
Leiden Genome Technology Center, Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
Search for more papers by this authorJohan T. den Dunnen
Leiden Genome Technology Center, Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
Search for more papers by this authorMarjo S. van der Knaap
Department of Child Neurology and VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Gajja S. Salomons
Metabolic Unit of the Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsSearch for more papers by this authorMarjan E. Steenweg
Department of Child Neurology and VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorCornelis Jakobs
Metabolic Unit of the Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorSilvy J.M. van Dooren
Metabolic Unit of the Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorMaria T. Adeva Bartolomé
Hospital Virgen del Puerto, Plasencia, Céceres, Spain
Search for more papers by this authorPeter Aerssens
Department of Pediatrics, Virga Jesse Hospital, Hasselt, Belgium
Search for more papers by this authorPersephone Augoustides-Savvapoulou
Department of Pediatrics-Metabolic Lab., Aristotle University of Thessaloniki, Hippocration General Hospital, Thessaloniki, Greece
Search for more papers by this authorIvo Baric
Department of Pediatrics, University Hospital Center, Zagreb, Croatia
Search for more papers by this authorMatthias Baumann
Department of Pediatrics, Division of Pediatric Neurology and Inherited Metabolic Disorders, Medical University of Innsbruck, Austria
Search for more papers by this authorLuisa Bonafé
Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanna, Switzerland
Search for more papers by this authorBrigitte Chabrol
Department of Metabolic Disease, Hospital Timone Enfants, Marseille, France
Search for more papers by this authorJoe T.R. Clarke
Division of Clinical & Metabolic Genetics, Hospital for Sick Children, Toronto, Canada
Search for more papers by this authorPeter Clayton
Department of Paediatric Metabolic Disease and Hepatology, Institute of Child Health, University College London, Great Ormond Street Hospital for Children, London, United Kingdom
Search for more papers by this authorMahmut Coker
Department of Pediatrics, Ege University Medical Faculty, Bornova, Izmir, Turkey
Search for more papers by this authorSarah Cooper
Department of Neurology, Southern General Hospital, Glasgow, United Kingdom
Search for more papers by this authorTzipora Falik-Zaccai
Institute of Human Genetics, Western Galilee Hospital, Naharia, Rappaport Faculty of Medicine, Haifa, Israel
Search for more papers by this authorMark Gorman
Department of Neurology, Children's Hospital Boston, Boston, Massachusetts
Search for more papers by this authorAndreas Hahn
Department of Pediatric Neurology, Giessen, Germany
Search for more papers by this authorAlev Hasanoglu
Department of Pediatric Metabolism and Nutrition, At Gazi University Faculty of Medicine, Turkey
Search for more papers by this authorMary D. King
Department of Pediatric Neurology, Children's University Hospital, Dublin, Ireland
Search for more papers by this authorHans B.C. de Klerk
Department of Pediatrics, Erasmus mc/Sophia Childrens Hospital Rotterdam, Rotterdam, The Netherlands
Search for more papers by this authorStanley H. Korman
Metabolic Disease Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Search for more papers by this authorCéline Lee
Children's Hospital, University of Bonn, Bonn, Germany
Search for more papers by this authorAllan Meldgaard Lund
Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark
Search for more papers by this authorVlatka Mejaški-Bošnjak
Department of Child Neurology, Children's Hospital Zagreb, Zagreb, Croatia
Search for more papers by this authorIgnacio Pascual-Castroviejo
Department of Pediatric Neurology, Hospital “La Paz,” Madrid, Spain
Search for more papers by this authorAparna Raadhyaksha
Medical Genetics, University of Miami, Florida
Search for more papers by this authorTerje Rootwelt
Division of Pediatrics, Rikshospitalet, Oslo University Hospital, Norway
Search for more papers by this authorAgathe Roubertie
CHU Montpellier, Department of Pediatric Neurology, Hospital Gui de Chauliac, Montpellier, France
Search for more papers by this authorMaria L. Ruiz-Falco
Department of Pediatric Neurology, Hospital Niño Jesús, Madrid, Spain
Search for more papers by this authorEmmanuel Scalais
Department of Pediatrics, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
Search for more papers by this authorManuel Seijo-Martinez
Department of Neurology, Hospital do Salnes, Villagarcia, Spain
Search for more papers by this authorMohnish Suri
Nottingham City Hospital, Clinical Genetics, Nottingham, United Kingdom
Search for more papers by this authorJolanta Sykut-Cegielska
Department of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland
Search for more papers by this authorFriedrich K. Trefz
Department of Pediatrics, Klinikum am Steinenberg, Reutlingen, Germany
Search for more papers by this authorGraziella Uziel
Child Neurology Department, National Institute for Neurology “Carlo Besta,” Milan, Italy
Search for more papers by this authorVassili Valayannopoulos
Department of Neuro-Metabolism, Hospital Necker Des Enfants Malades, Paris, France
Search for more papers by this authorChristine Vianey-Saban
Centre de Biotechnology Cellulaire, Hopital Debrousse, Lyon, France
Search for more papers by this authorStefan Vlaho
Department of Pediatric Neurology, Klinik für Kinder-und Jugendmedizin, Johann Wolfgang Goethe-University, Frankfurt, Germany
Search for more papers by this authorJulia Vodopiutz
Department for Inborn Errors of Metabolism and Pediatric Genetics, University Children's Hospital Vienna, Vienna, Austria
Search for more papers by this authorMoacir Wajner
Department of Medical Genetics, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brasil
Search for more papers by this authorJohn Walter
Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom
Search for more papers by this authorClaudia Walter-Derbort
Department of Pediatrics, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany
Search for more papers by this authorZuhal Yapici
Department of Neurology, Istanbul University, Faculty of Medicine, Istanbul, Turkey
Search for more papers by this authorDimitrios I. Zafeiriou
Department of Child Neurology and Developmental Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece
Search for more papers by this authorMarieke D. Spreeuwenberg
Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorJacopo Celli
Leiden Genome Technology Center, Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
Search for more papers by this authorJohan T. den Dunnen
Leiden Genome Technology Center, Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
Search for more papers by this authorMarjo S. van der Knaap
Department of Child Neurology and VU University Medical Center, Amsterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Gajja S. Salomons
Metabolic Unit of the Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsSearch for more papers by this authorCommunicated by Ronald Wanders
Abstract
L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype–genotype relationship. Hum Mutat 30:1–11, 2010. © 2010 Wiley-Liss, Inc.
Supporting Information
Additional Supporting information may be found in the online version of this article
| Filename | Description |
|---|---|
| humu_21197_sm_SupplInfo1.pdf16.3 KB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Abramson CJ, Platt SR, Jakobs C, Verhoeven NM, Dennis R, Garosi L, Shelton GD. 2003. L-2-hydroxyglutaric aciduria in Staffordshire Bull terriers. J Vet Intern Med 17: 551–556.
- Aghili M, Zahedi Z, Rafiee E. 2009. Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review. J Neurooncol 91: 233–236.
- Barbot C, Fineza I, Diogo L, Maia M, Melo J, Guimarães A, Pires MM, Cardoso ML, Vilarinho L. 1997. L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients. Brain Dev 19: 268–273.
- Barth PG, Hoffmann GF, Jaeken JJ, Lehnert W, Hanefeld F, van Gennip AH, Duran M, Valk J, Schutgens RB, Trefz FK, Reimann G, Hartung HP. 1992. L-2-Hydroxyglutaric aciduria: a novel inherited neurometabolic disease. Ann Neurol 32: 66–71.
- Barth PG, Hoffmann GF, Jaeken J, Wanders RJA, Duran M, Jansen GA, Jakobs C, Lehnert W, Hanefeld F, Valk J, Schutgens RBH, Trefz FK, Hartung HP, Chamoles NA, Sfaello Z, Caruso U. 1993. L-2-Hydroxyglutaric acidaemia: clinical and biochemical findings in 12 patients and preliminary report on L-2-hydroxyacid dehydrogenase. J Inherit Metab Dis 16: 753–761.
- Burge C, Karlin S. 1997. Prediction of complete gene structures in human genomic DNA. J Mol Biol 268: 78–94.
- da Silva CG, Bueno ARF, Schuck PF, Leipnitz G, Ribeiro CAJ, Wannmacher CMD, Wyse ATS, Wajner M. 2003. L-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats. Int J Dev Neurosci 21: 217–224.
- den Dunnen JT, Antonarakis SE. 2000. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15: 7–12
- D'Incerti L, Farina L, Moroni I, Uziel G, Savoiardo M. 1998. L-2-Hydroxyglutaric aciduria: MRI in seven cases. Neuroradiology 40: 727–733.
- Duran M, Kamerling JP, Bakker HD, van Gennip AH, Wadman SK. 1980. L-2-Hydroxyglutaric aciduria: an inborn error of metabolism? J Inherit Metab Dis 3: 109–112.
- Fokkema IF, den Dunnen JT, Taschner PE. 2005. LOVD: easy creation of a locus-specific sequence variation database using an “LSDB-in-a-box” approach. Hum Mut 26: 63–68.
- Fujitake J, Ishikawa Y, Fuji H, Nishimura K, Hayakawa K, Inoue F, Terada N, Okochi M, Tatsuoka Y. 1999. L-2-Hydroxyglutaric aciduria: two Japanese adult cases in one family. J Neurol 246: 378–382.
- Garosi GS, Penderis J, McConnell JF, Jakobs C. 2005. L-2-Hydroxyglutaric aciduria in a West Highland white terrier. Vet Rec 156: 145–147.
- Goffette SM, Duprez TP, Nassogne MCL, Vincent MFA, Jakobs C, Sindic CJ. 2006. L-2-Hydroxyglutaric aciduria: clinical, genetic, and brain MRI characteritics in two adult sisters. Eur J Neurol 13: 499–504.
- Haliloglu G, Jobard F, Oguz KK, Anlar B, Akalan N, Coskun T, Sass JO, Fischer J, Topcu M. 2008. L-2-Hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings. Neuropediatrics 39: 119–122.
- Hall TA. 1999. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41: 95–98.
- Jequier Gygax M, Roulet-Perez E, Meagher-Villemure K, Jakobs C, Salomons GS, Boulat O, Superti-Furga A, Ballhausen D, Bonafé L. 2009. Sudden unexpected death in an infant with L-2-hydroxyglutaric aciduria. Eur J Pediatr 168: 957–962.
- Junqueira D, Brusque AM, Porciúncula LO, Rotta LN, Ribeiro CAJ, Frizzo MES, Dutra Filho CS, Wannmacher CMD, Wyse ATS, Souza DO, Wajner M. 2003. Effects of L-2-hydroxyglutaric acid on various parameters of the glutamatergic system in cerebral cortex of rats. Metab Brain Dis 18: 233–243.
- Larnaout A, Amouri R, Kefi M, Hentati F. 2008. L-2-Hydroxyglutaric aciduria: clinical and molecular study in three tunesian families. Identification of a new mutation and inter-familial phenotype variability. J Inherit Metab Dis [Epub ahead of print].
- Latini A, Scussiato K, Rosa RB, Leipnitz G, Llesuy S, Belló-Klein A, Dutra-Filho CS, Wajner M. 2003. Induction of oxidative stress by L-2-hydroxyglutaric acid in rat brain. J Neurosci Res 74: 103–110.
- Moroni I, Bugiani M, D'Incerti L, Maccagnano C, Rimoldi M, Bissola L, Pollo B, Inocchiaro G, Uziel G. 2004. L-2-Hydroxyglutaric aciduria and brain malignant tumors: a predisposing condition? Neurology 62: 1882–1884.
- Moroni I, D'Incerti L, Farina L, Rimoldi M, Uziel G. 2000. Clinical, biochemical and neuroradiological findings in L-2-hydroxyglutaric aciduria. Neurol Sci 21: 103–108.
- O'Conner G, King M, Salomons G, Jakobs C, Hardiman O. 2009. A novel mutation as a cause of L-2-hydroxuglutaric aciduria. J Neurol [Epub ahead of print].
- Penderis J, Calvin J, Abramson C, Jakobs C, Pettitt L, Binns MM, Verhoeven NM, O'Driscoll E, Platt SR, Mellersh CS. 2007. L-2-hydroxyglutaric aciduria: characterization of the molecular defect in a spontaneous canine model. J Med Genet 44: 334–340.
- Reese MG, Eeckman FH, Kulp D, Haussler D. 1997. Improved splice site detection in genie. J Comp Biol 4: 311–323.
- Rzem R, Van Schaftingen E, Veiga-da-Cunha M. 2006. The gene mutated in L-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase. Biochimie 88: 113–116.
- Rzem R, Veiga-da-Cunha M, Noel G, Goffette S, Nassogne MC, Tabarki B, Schöller C, Marquardt T, Vikkula M, van Schaftingen E. 2004. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc Natl Acad Sci USA 101: 16849–16854.
- Rzem R, Vincent MF, Van SE, Veiga-da-Cunha M. 2007. L-2-Hydroxyglutaric aciduria, a defect of metabolite repair. J Inherit Metab Dis 30: 681–689.
- Samuraki M, Komai K, Hasegawa Y, Kimura M, Yamaguchi S, Terada N, Yamada M. 2008. A successfully treated adult patient with L-2-hydroxyglutaric aciduria. Neurology 70: 1051–1052.
- Sass JO, Jobard F, Topcu M, Mahfoud A, Werle E, Cure S, Al-Sannaa A, Alshahwan SA, Bataillard M, Cimbalistiene L, Grolik C, Kemmerich V, Omran H, Sztriha L, Tabache M, Fischer J. 2008. L-2-Hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene. J Inherit Metab Dis [Epub ahead of print].
- 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: 666–670.
- Steenweg ME, Salomons GS, Yapici Z, Uziel G, Scalais E, Zafeiriou DI, Ruiz-Falco ML, Mejaski-Bosnjak V, Augoustides-Savvopoulou P, Wajner M, Walter J, Verhoeven-Duif NM, Struys EA, Jakobs C, van der Knaap MS. 2009. L-2-Hydroxyglutaric aciduria: pattern of MR Imaging abnormalities in 56 patients. Radiology 251: 856–865.
- Struys EA, Gibson KM, Jakobs C. 2007. Novel insights into L-2-hydroxyglutaric aciduria: mass isotopomer studies reveal 2-oxoglutaric acid as the metabolic precursor of L-2-hydroxyglutaric acid. J Inherit Metab Dis 30: 690–693.
- Struys EA, Jansen EE, Verhoeven NM, Jakobs C. 2004. Measurement of urinary D- and L-2-hydroxyglutarate enantiomers by stable-isotope-dilution liquid chromatography-tandem mass spectrometry after derivatization with diacetyl-L-tartaric anhydride. Clin Chem 50: 1391–1395.
- Topcu M, Aydin OF, Yalcinkaya C, Haliloǧlu G, Aysun S, Anlar B, Topaloǧlu H, Turanli G, Yalnizogǧlu D, Kesimer M, Coşkun T. 2005. L-2-Hydroxyglutaric aciduria: a report of 29 patients. Turk J Pediatr 47: 1–7.
- Topcu M, Jobard F, Halliez S, Coskun T, Yalçinkayal C, Ozbas Gerceker F, Wanders RJA, Prud'homme, Lathrop M, Özguc M, Fischer J. 2004. L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1. Hum Mol Genet 13: 2803–2811.
- Van Schaftingen E, Rzem R, Veigha-da-Cunha M. 2009. L-2-Hydroxyglutaric aciduria, a disorder of metabolite repair. J Inherit Metab Dis. 32: 135–142.
- Vilarinho L, Cardoso ML, Gaspar P, Barbot C, Azevedo L, Diogo L, Santos M, Carrilho I, Fineza I, Kok F, Chorão R, Alegria P, Martins E, Teixeira J, Cabral Fernandes H, Verhoeven NM, Salomons GS, Santorelli FM, Cabral P, Amorim A, Jakobs C. 2005. Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin. Hum Mutat 26: 395–396.
- Wilcken B, Pitt J, Heath D, Walsh P, Wilson G, Buchanan N. 1993. L-2-hydroxyglutaric aciduria: three Australian cases. J Inherit Metab Dis 16: 501–504.
- Wildeman M, van Ophuizen E, den Dunnen JT, Taschner PE. 2008. Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker. Hum Mut 29: 6–13.
- Yilmaz K. 2009. Riboflavin treatment in a case with L-2-hydroxyglutaric aciduria. Eur J Paediat Neurol 13: 57–60.
- Zafeiriou DI, Ververi A, Salomons GS, Vargiami E, Haas D, Papadopoulou V, Kontopoulos E, Jakobs C. 2008. L-2-hydroxyglutaric aciduria presenting with severe autistic features. Brain Dev 30: 305–307.
