Journal of Inherited Metabolic Disease

, Volume 22, Issue 4, pp 404–413

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
Article

DOI: 10.1023/A:1005548005393

Cite this article as:
van der Knaap, M.S., Jakobs, C., Hoffmann, G.F. et al. J Inherit Metab Dis (1999) 22: 404. doi:10.1023/A:1005548005393

Abstract

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.

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • M. S. van der Knaap
    • 1
  • C. Jakobs
    • 2
  • G. F. Hoffmann
    • 3
  • M. Duran
    • 4
  • A. C. Muntau
    • 5
  • S. Schweitzer
    • 6
  • R. I. Kelley
    • 7
  • F. Parrot-Roulaud
    • 8
  • J. Amiel
    • 9
  • P. De Lonlay
    • 9
  • D. Rabier
    • 10
  • O. Eeg-Olofsson
    • 11
  1. 1.Department of Child NeurologyFree University HospitalAmsterdamThe Netherlands
  2. 2.Metabolic Unit of the Department of Clinical ChemistryFree University HospitalAmsterdamThe Netherlands
  3. 3.Department of Neuropediatrics and Metabolic DiseasesKinderklinik der Philipps-UniversitätMarburgGermany
  4. 4.Division of Metabolic DiseasesUniversity Children's HospitalUtrechtThe Netherlands
  5. 5.Metabolic DepartmentDr von Haunersches Kinderspital, Universität MünchenMünchenGermany
  6. 6.KinderklinikUniversity HospitalHanoverGermany
  7. 7.Department of NeurogeneticsKennedy Krieger InstituteBaltimoreUnited States
  8. 8.Laboratoire de Biochimie, Département Malades MetaboliquesHôpital PellegrinBordeauxFrance
  9. 9.Service de Génétique MédicaleHôpital Necker Enfants MaladesParisFrance
  10. 10.Laboratoire de Biochimie MédicaleHôpital Necker Enfants MaladesParisFrance
  11. 11.Department of PediatricsUniversity Children's HospitalUppsalaSweden

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