Journal of Inherited Metabolic Disease

, Volume 19, Issue 3, pp 335–343

l-2-Hydroxyglutaric aciduria: Neuropathological correlations and first report of severe neurodegenerative disease and neonatal death

  • E. Chen
  • W. L. Nyhan
  • C. Jakobs
  • C. M. Greco
  • A. J. Barkovich
  • V. A. Cox
  • S. Packman
Article

DOI: 10.1007/BF01799264

Cite this article as:
Chen, E., Nyhan, W.L., Jakobs, C. et al. J Inherit Metab Dis (1996) 19: 335. doi:10.1007/BF01799264

Summary

l-2-Hydroxyglutaric aciduria is a rare organic aciduria associated with neurological and particularly cerebellar abnormalities. These abnormalities developed in childhood or later in all previously described patients. We report a more severe form ofl-2-hydroxyglutaric aciduria in which an infant presented shortly after birth with hypotonia, apnoea, and seizures, leading to death in the perinatal period. Computerized tomography scans of the brain at 1 day and 2 weeks of age showed abnormal low density of the cerebellum. Examination of the brain showed brainstem and cerebellar atrophy with neuronal loss and gliosis in an olivopontocerebellar distribution. The diagnosis ofl-2-hydroxyglutaric aciduria should be considered in any non-dysmorphic newborn with progressive neurological abnormalities and CNS imaging suggesting low density and size of the cerebellum. The diagnostic consideration is based initially on clinical findings. Conventional urine organic acid analysis reveals the presence of 2-hydroxyglutaric aciduria. Specific diagnosis requires methodologies which distinguish thel- from thed-isomer.

Copyright information

© SSIEM and Kluwer Academic Publishers 1996

Authors and Affiliations

  • E. Chen
    • 1
  • W. L. Nyhan
    • 2
  • C. Jakobs
    • 6
  • C. M. Greco
    • 5
  • A. J. Barkovich
    • 3
  • V. A. Cox
    • 4
  • S. Packman
    • 4
  1. 1.Department of Medical GeneticsChildren's Hospital OaklandOakland
  2. 2.Department of PediatricsDivision of Biochemical GeneticsUSA
  3. 3.Department of RadiologyDivision of Medical Genetics, University of CaliforniaSan Francisco
  4. 4.Division of Medical Genetics, Department of PediatricsUCSF Medical CenterSan FranciscoUSA
  5. 5.Department of PathologyCalifornia Pacific Medical CenterSan FranciscoUSA
  6. 6.Department of PediatricsFree University HospitalAmsterdamThe Netherlands

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