Adult manifestation of l -2-hydroxyglutarate dehydrogenase deficiency by a novel mutation

Abstract

l-2-Hydroxyglutaric aciduria (L2HGA) is a rare, autosomal recessive disease caused by a deficiency of l-2-hydroxyglutarate dehydrogenase (L2HGDH). This membrane-bound mitochondrial enzyme is prominently expressed in the brain1 and catalyzes the conversion of l-2-hydroxyglutaricacid (L2HG) to 2-ketoglutarate. The exact function is unknown, but the lack of L2HGDH is toxic by inducing oxidative stress and inhibiting mitochondrial creatine kinase in the cerebellum.2 Commonly, symptoms appear during infancy as slowly progressing deficits including psychomotor retardation, cerebellar ataxia, and epilepsy3; however, an acute worsening in adulthood has been described.4 A diagnosis can be achieved through the detection of elevated L2HG in the urine3,5 and although no treatment guidelines exist, positive effects were reported following treatment with flavin adenine dinucleotide in combination with levocarnitine or riboflavin.6,7 We report the case of a young woman with L2HGA, presenting with a fast progressive cerebellar syndrome that could be halted by a low lysine diet. ### Case report. A 24-year-old patient presented with a progressive movement disorder and a disabling tremor of the right hand that began 1.5 years ago. Her mother reported delayed motor and mental development …