Riboflavin treatment in L-2-hydroxyglutaric aciduria: report on a pediatric patient and literature review.

Abstract

L-2-hydroxyglutaric aciduria (L-2-HGA, #236,792) is an autosomal recessive neurodegenerative disorder caused by the deficiency of L-2-hydroxyglutarate dehydrogenase, a flavin adenine dinucleotide (FAD)-dependent enzyme, due to biallelic pathogenic variants in the L2HGDH gene. The present study described the patient with L2HGA presenting with a slight psychomotor delay, epilepsy from 5 years of age, non-progressive cerebellar ataxia, and mild to moderate intellectual disability during 10 years of follow-up. Two different heterozygous variants in the L2HGDH gene were identified in the patient: a known substitution c.829C > T(p.Arg277*) and a novel substitution c.1196 + 1G > A corresponding with significantly increased urinary L-2-hydroxyglutarate (L2HG) excretion. A 6-month period of treatment with riboflavin (100 mg/day) was implemented with no clinical nor biochemical effect.