l-2-Hydroxyglutaric aciduria: Neuropathological correlations and first report of severe neurodegenerative disease and neonatal death
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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.
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Journal of Inherited Metabolic Disease
Volume 19, Issue 3 , pp 335-343
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- Kluwer Academic Publishers
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- 1. Department of Medical Genetics, Children's Hospital Oakland, Oakland, California
- 2. Department of Pediatrics, Division of Biochemical Genetics, USA
- 3. Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands
- 4. Department of Pathology, California Pacific Medical Center, San Francisco, California, USA
- 5. Department of Radiology, Division of Medical Genetics, University of California, San Francisco
- 6. Division of Medical Genetics, Department of Pediatrics, UCSF Medical Center, Campus Box 0748, 94143, San Francisco, CA, USA