l-2-Hydroxyglutaric aciduria presenting with severe autistic features

l-2-Hydroxyglutaric aciduria (l-2-HGA) is an autosomal recessive neurometabolic disorder characterized by psychomotor delay, ataxia, macrocephaly and typical neuroradiological findings of subcortical leucoencephalopathy. Recently, the disease causing gene has been discovered (L2HGDH) encoding l-2-hydroxyglutarate dehydrogenase. We present a 3-year-old boy with l-2-HGA, who demonstrated macrocephaly, noted already in utero with ultrasound. Cranial MRI demonstrated diffuse subcortical encephalopathy with increased signal of the subcortical white matter. Subsequent metabolic screening revealed increased levels of l-2-HGA, and genomic DNA analysis demonstrated two missense mutations in l-2-HGDG. Patient’s further motor development was mildly impaired, whilst his speech development was profoundly impaired (first words at the age of 2 years). Since the age of 2 years he started demonstrating autistic repetitive behaviors and movements, increasing aloofness to his environment and limitations in the variety of spontaneous activity (CARS score: 44/60-severe autism). Autism has not so far been described in l-2-HGA and may be considered as an additional feature of the phenotypic spectrum.