D-2-hydroxyglutaric aciduria: Further clinical delineation

M. S. Van Der Knaap, C. Jakobs, G. F. Hoffmann, M. Duran, A. C. Muntau, S. Schweitzer, R. I. Kelley, F. Parrot-Roulaud, J. Amiel, P. De Lonlay, D. Rabier, O. Eeg-Olofsson

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


It has recently been recognized that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with a severe and a mild phenotype. Whereas the clinical and neuroimaging findings of the severe phenotype were homogeneous among the patients, the findings in the mild phenotype were much more variable, leaving the clinical picture poorly defined. We were able to collect the clinical, biochemical and neuroimaging data on an additional 8 patients 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 phenotype shares the essential characteristics of the severe phenotype. The most frequent findings, regardless of the clinical phenotype, are epilepsy, hypotonia and psychomotor retardation. Additional findings, mainly occurring in the severe phenotype, are episodic vomiting, cardiomyopathy, inspiratory stridor and apnoeas. The most consistent MRI finding is enlargement of the lateral ventricles, occipital more than frontal. Regardless of the clinical phenotype, early MRI shows in addition subependymal cysts and signs of delayed cerebral maturation. Later MRI may reveal multifocal cerebral white-matter abnormalities. Two patients had vascular abnormalities, but it is as yet unclear whether these are related to D-2-hydroxyglutaric aciduria or are incidental findings.

Original languageEnglish (US)
Pages (from-to)404-413
Number of pages10
JournalJournal of Inherited Metabolic Disease
Issue number4
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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