D-2-hydroxyglutaric aciduria: hypotonia, cortical blindness, seizures, cardiomyopathy, and cylindrical spirals in skeletal muscle

Abstract

An infant girl was demonstrated to have D-2-hydroxyglutaric aciduria, the fifth case described and the first with muscle biopsy of this rare organic aciduria that differs clinically and genetically from the more common L-2-hydroxyglutaric aciduria. Her clinical features included mildly dysmorphic facies, developmental delay, generalized hypotonia, myoclonic seizures, cortical blindness, and dilated cardiomyopathy requiring treatment. Muscle biopsy demonstrated only excessive glycogen histochemically, but ultrastructural examination revealed subsarcolemmal cylindrical spirals and normal mitochondria. Because of the metabolism of D-2-hydroxyglutaric aciduria, we regard valproic acid as contraindicated in the treatment of epilepsy in this disease.