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l ‐2‐Hydroxyglutaric aciduria: Neuropathological correlations and first report of severe neurodegenerative disease and neonatal death
Author(s) -
Chen E.,
Nyhan W. L.,
Jakobs C.,
Greco C. M.,
Barkovich A. J.,
Cox V. A.,
Packman S.
Publication year - 1996
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799264
Subject(s) - gliosis , cerebellum , hypotonia , medicine , pathology , brainstem , atrophy , central nervous system , central nervous system disease , degenerative disease , pediatrics , disease , endocrinology
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 of l ‐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 of l ‐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 the l ‐ from the d ‐isomer.