L-2-Hydroxyglutaric aciduria: a case report.

Introduction: L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disease with a slowly progressive course and characterized by increased levels of hydroxyglutaric acid in urine, cerebrospinal fluid and plasma. In this condition clinical features mainly consist of mental deterioration, ataxia and motor deficits.

Case Outline: The patient is a 16-year-old girl, the first and only child of healthy, non-consanguineous parents of Serbian origin. At the age of 4 years her walk became unsteady and ataxic. Other signs of cerebellar involvement were soon observed. Head circumference was above two standard deviations (55 cm). Mild mental retardation was revealed by formal intelligence testing (IQ 60). MR examination of the brain showed confluent subcortical white matter lesions spread centripetally, and atrophy of the cerebellar vermis with involvement of dentate nuclei, without deep white matter abnormalities. Laboratory investigation revealed increased amounts and a very large peak of HGA in urine and plasma. Enantiomeric analysis confirmed the L-configuration (> 90%) establishing the diagnosis of L-2-HGA. The first epileptic seizure, partial with secondary generalization, occurred at age of 8 years. Favorable seizure control was achieved. A slow progression of neurological impairment was noted. Therapeutic trials with oral coenzyme Q10 and with oral riboflavin showed no biochemical and clinical effects. Recently, the diagnosis was proven by the presence of a mutation in the L-2-HGA gene.

Conclusion: To our knowledge, this is the first report of L-2-HGA in Serbia. L-2-HGA must be considered in the differential diagnosis based on specific findings in cranial MRI.