[D-2-hydroxyglutaric aciduria. Report of two cases]

Abstract

D-2-hydroxyglutaric aciduria (D-2-HGA) is a cerebral organic aciduria characterized by the accumulation of abnormal amounts of D-2-hydroxyglutaric acid in cerebrospinal fluid, blood, and urine. The clinical phenotype varies widely from neonatal severe epileptic encephalopathy to asymptomatic. Magnetic resonance imaging of affected patients typically show signs of delayed cerebral maturation, ventricular abnormalities and the presence of sub-ependymal cysts in the first months of life. We present clinical, biochemical and brain magnetic resonance imaging data of two pediatric patients with D-2-hydroxyglutaric aciduria. One patient presented with severe early infantile-onset epileptic encephalopathy, marked hypotonia, visual deficit, developmental delay and abnormal neuroradiological findings; while the other had hypotonia and development delay. Our findings reinforce the described phenotype of this rare neurometabolic inherited disorder. The diagnostic approach is based on clinical findings and the neuroimaging pattern and is established by the detection of D-2-hydroxyglutaric acid in body fluids. We suggest considering D-2-hydroxyglutaric aciduria in the differential diagnosis of any neonate or infant with epileptic encephalopathy and CNS dysfunction of unknown origin.