DIAGNOSIS AND MANAGEMENT OF GLUTARIC ACIDURIA TYPE-I

Glutaric aciduria type I (GA1) is a preventable cause of acute brain d amage in early childhood, leading to a severe dystonic-dyskinetic diso rder that is similar to cerebral palsy and ranges from extreme hypoton ia to choreoathetosis to rigidity with spasticity. Degeneration of the putamen and caudate typically occurs between 6 and 18 months of age a nd is probably linked to changes in metabolic demand caused by normal maturational changes and superimposed catabolic stress. Recognition of this biochemical disorder before the brain has been injured is essent ial to outcome. Diagnosis depends upon the recognition of relatively n onspecific physical findings such as hypotonia, irritability and macro cephaly, and on performance of urine organic acid quantification by ga s chromatography-mass spectrometry or selective searches of urine or b lood specimens by tandem mass spectrometry for glutarylcarnitine. The diagnosis may also be suggested by characteristic findings on neuroima ging. In selected patients diagnosis can only be reached by enzyme ass ay. Specific current management by the authors of this paper includes pharmacological doses of L-carnitine, as well as dietary protein restr iction. Metabolic decompensation must be treated aggressively to avoid permanent brain damage. Multicentre studies are needed to establish b est methods of diagnosis and optimal therapy of this disorder.