title: White matter abnormalities in an adult patient with l-2-hydroxyglutaric aciduria.
abstract: l-2-Hydroxyglutaric aciduria (l-2-HGA) is a rare inborn error of metabolism. Mainly, patients with this disorder exhibit neurological symptoms and characteristic neuroradiological findings, such as subcortical white matter abnormalities, which are believed to be caused by the toxicity of the accumulation of l-2-hydroxyglutaric acid. A genotype-first approach of the whole exome sequence was used to identify compound heterozygous mutations, c.584A>G (p.Y195C) and c.772T>C (p.C258R), in L2HGDH, the gene responsible for this disorder, in an adult patient with intellectual disability and intractable epilepsy. A retrospective assay confirmed the increased concentrations of 2-hydroxyglutaric acid in the urine. These results suggested that neuroradiological findings of subcortical white matter abnormalities are characteristic of l-2-HGA and that clinical exome sequencing has sufficient power to compensate for insufficient clinical evaluations.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Shiga Medical University, Ohtsu, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yoshioka
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shimada
authors.initials: S
authors.lastname: Shino
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Health Science, Faculty of Medical Sciences, University of Fukui, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shigematsu
authors.affiliation: Department of Pediatrics, Shiga Medical University, Ohtsu, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics* / Q000473:pathology* / Q000652:urine; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D012189:Retrospective Studies; D017386:Sequence Homology, Amino Acid; D066127:White Matter / Q000473:pathology*
chemical_list: D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human
keywords: Clinical exome sequencing; Genotype-first approach; L2HGDH; Subcortical white matter abnormalities; l-2-Hydroxyglutaric aciduria (l-2-HGA)