D-2-hydroxyglutaric aciduria: Further clinical delineation

It has recently been recognized that D-2-hydroxyglutaric aciduria is a dist inct neurometabolic disorder with a severe and a mild phenotype. Whereas th e clinical and neuroimaging findings of the severe phenotype were homogeneo us among the patients, the findings in the mild phenotype were much more va riable, leaving the clinical picture poorly defined. We were able to collec t the clinical, biochemical and neuroimaging data on an additional 8 patien ts with D-2-hydroxyglutaric aciduria, 4 with the severe and 4 with the mild phenotype. With the new information, it becomes clear that the mild phenot ype shares the essential characteristics of the severe phenotype. The most frequent findings, regardless of the clinical phenotype, are epilepsy, hypo tonia and psychomotor retardation. Additional findings, mainly occurring in the severe phenotype, are episodic vomiting, cardiomyopathy, inspiratory s tridor and apnoeas. The most consistent MRI finding is enlargement of the l ateral ventricles, occipital more than frontal. Regardless of the clinical phenotype, early MRI shows in addition subependymal cysts and signs of dela yed cerebral maturation. Later MRI may reveal multifocal cerebral white-mat ter abnormalities. Two patients had vascular abnormalities, but it is as ye t unclear whether these are related to D-2-hydroxyglutaric aciduria or are incidental findings.