title: L-2-Hydroxyglutaric aciduria presenting with severe autistic features.
abstract: 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.
authors.affiliation: 1st Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece. jeff@med.auth.gr
authors.forename: D I
authors.initials: DI
authors.lastname: Zafeiriou
authors.forename: A
authors.initials: A
authors.lastname: Ververi
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
authors.forename: E
authors.initials: E
authors.lastname: Vargiami
authors.forename: D
authors.initials: D
authors.lastname: Haas
authors.forename: V
authors.initials: V
authors.lastname: Papadopoulou
authors.forename: E
authors.initials: E
authors.lastname: Kontopoulos
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000235:genetics* / Q000652:urine; D001321:Autistic Disorder / Q000209:etiology* / Q000235:genetics* / Q000652:urine; D001921:Brain / Q000473:pathology; D005977:Glutarates / Q000652:urine*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human