Normal pregnancy outcome in L‐2‐hydroxyglutaric aciduria

Abstract

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare progressive neurometabolic disease, defined as a characteristic clinical and radiological entity, mainly including mental retardation, cerebellar dysfunction and involvement of the subcortical white matter, cerebellum and basal ganglia on brain MRI. The biochemical hallmark is an increased urinary excretion of L-2-hydroxyglutaric acid. Management is only supportive. A child born to a Turkish mother in whom L-2-HGA was previously diagnosed is reported. Although pregnancy was repeatedly advised against because of the important degree of mental retardation and the potential risk of a toxic effect on the embryo and/or fetus (at that time no reports of maternal L-2-HGA were available), she became pregnant at 30 years of age and the pregnancy passed uneventfully. On amniocentesis, performed at 5 months of gestational age, elevated 2-hydroxyglutarate, previously shown to be almost exclusively the L-2-stereoisomer, was present in the amniotic fluid: 27.5mu mol/L (controls <1.3; n=5). The child, not affected by the disease as shown by a normal urinary excretion of 2-hydroxyglutaric acid, was normal at birth. When last examined at the age of 3 years, both somatic and mental development were excellent. As the pathogenesis of the extensive brain damage in affected persons remains largely unknown, notwithstanding the recent identification of the mutated gene and the deficient enzyme, one can only speculate on the mechanism by which embryo and fetus from a L-2-HGA mother are spared, at least in this case.