A rare progressive neurometabolic disease (L-2-hydroxyglutaric aciduria) diagnosed by urinary organic acid analysis

Background: L-2-Hydroxyglutaric aciduria is a rare inborn error of metabolism characterised clinically by ataxia, psychomotor delay and epilepsy and biochemically by increased urinary excretion of L-2-hydroxyglutaric acid. The disease was first described by Duran et al in 1980.

Patients and methods: The patient (now aged 9.5 years), the 1^st? child of non-consanguineous (Ethiopian?) parents, presented with psychomotor retardation, ataxia (especially with dysartria and dysmetria) and epilepsy. In the neonatal period, he suffered from severe apnoeic episodes. Differential diagnostic workup revealed highly increased urinary 2-hydroxyglutaric acid and enantiomeric analysis confirmed the L-configuration. MRI of the brain showed typical signs of leucomalacia, with increased periventricular spaces and cerebellar atrophy. Until now, all described patients have been of Saudi Arabian, Irani, Iraqi or Serbian descent. Three patients have been found in Australia, but African patients have not been reported. There is no causal therapy of this disease. Alle Patienten zeigen eine Makrocephalie – sehr wichtig – DD: GA1, Canavan, L-2 HydroxyGA!!!

Conclusion: L-2-Hydroxyglutaric aciduria is an inherited neurometabolic disease with clinical signs of ataxia, retardation and epilepsy increased urinary excretion of L-2-hydroxyglutaric acid.

The final diagnosis requires enantiomeric analysis to confirm the L-configuration.

Patients with non-familial macrocephaly, ataxia and progressive neurodegeneration should undergo urinary organic acid analysis. As only palliative therapy exists for this disorder, a molecular genetic investigation should be undertaken to provide counselling for the affected family