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.
Keywords: Clinical exome sequencing; Genotype-first approach; L2HGDH; Subcortical white matter abnormalities; l-2-Hydroxyglutaric aciduria (l-2-HGA).
Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.