L-2-hydroxyglutaric aciduria caused by a new mutation in the L2HGDH gene

Abstract

The authors present a case-report of 13 year-old girl with L-2-hydroxyglutaric aciduria [MIM#236792], a rare autosomal/recessive metabolic disorder caused by mutations in the L-encoding 2-hydroxyglutarate dehydrogenase (L2HGDH, 14q21.3). Clinical signs of the disease are presented by predominantly neurological symptoms (epilepsy, cerebellar ataxia, cognitive impairment). The distinctive feature is the specific multifocal lesion of the white matter detected on MRI. The characteristic neuroimaging picture and positive results of biochemical and molecular genetic diagnosis were identified.

Beyond Isocitrate Dehydrogenase Mutations: Emerging Mechanisms for the Accumulation of the Oncometabolite 2-Hydroxyglutarate

“…L2HGDH and D2HGDH are responsible for the clearance of L-2-HG and D-2-HG, respectively. L2HGDH or D2HGDH mutation has been identified to be the cause of 2-HG accumulation in L-2HGA and D-2HGA, respectively. , Mutation of L2HGDH or D2HGDH resulted in its inability to bind the FAD cofactor and its failure to catalyze 2-HG back to αKG. , 2HGA patients exhibit a great increase in 2-HG in plasma, cerebrospinal fluid, and urine resulting from impaired 2-HG clearance. , In addition, impaired L2HGDH function to remove L-2-HG has also been found in RCC with L2HGDH expression decrease. In RCC, 2-HG was accumulated to micromolar concentration.…”

“…40,41 2HGA patients exhibit a great increase in 2-HG in plasma, cerebrospinal fluid, and urine resulting from impaired 2-HG clearance. 41,42 In addition, impaired L2HGDH function to remove L-2-HG has also been found in RCC with L2HGDH expression decrease. In RCC, 2-HG was accumulated to micromolar concentration.…”