L-2-hydroxyglutaric aciduria: a report of six cases and review of the literature.

L-2-hydroxyglutaric aciduria is a rare and novel autosomal recessive inherited neurometabolic disorder. Since its first description by Duran in 1980, less than 100 cases have so far been reported. Occurring mostly in childhood, it is characterized by slowly progressive neurological dysfunction with cerebellar ataxia, pyramidal signs, intellectual decline, seizure, and extrapyramidal symptoms. MRI scanning is highly characteristic and screening for organic acid (L-2-hydroxyglutaric acid) in urine, serum, and cerebrospinal fluid is diagnostic. We investigated six Iranian children, aged 4, 14, 16, and 16 years, (the last one had two affected brothers and both of them died of similar illness at the ages of 20 and 22), by urinary organic acids assay and MRI scanning with suspicion of this rare disorder. Symptoms were suspicious for one of the leukoencephalopathies accompanied by macrocephaly. Affected cases were evaluated because of mild to moderate psychomotor retardation and regression. Head circumferences were above 2 standard deviations. Urine levels of L-2-hydroxyglutaric acid were strongly increased. MRI scanning of the brain showed hyperintense signal on T2W images of the subcortical white matter and basal ganglia in all of them. Because of its inheritance pattern (autosomal recessive) and the high rate of consanguineous marriages in Iran, the prevalence of this disorder might be high among the mentally-handicapped patients, especially those with macrocephaly. Therefore, this entity should be considered in the differential diagnosis of mentally-retarded patients with macrocephaly.