DYSTONIA AND DYSKINESIA IN GLUTARIC ACIDURIA TYPE-I - CLINICAL HETEROGENEITY AND THERAPEUTIC CONSIDERATIONS

Glutaric aciduria type I (GA-I) is an inborn error in the degradation of lysine, hydroxylysine, and tryptophan due to a deficiency of glutar yl-CoA dehydrogenase. Glutaric, 3-OH-glutaric, and glutaconic acids ar e excreted in the urine, particularly during intercurrent illness. The enzyme may be assayed in leukocytes, cultured fibroblasts and chorion ic villi. Twelve new cases, 9 months-16 years of age, are reported, co mprising all known cases of GA-I in Sweden and Norway. Ten had a sever e dystonic-dyskinetic disorder, one had a mild hyperkinetic disorder, and one was asymptomatic. Two children died in a state of hyperthermia . Carnitine deficiency and malnutrition developed in patients with sev ere dystonia and dysphagia, which necessitated substitution and gastro stomy. A slowly progressive dyskinetic disorder developed in spite of adequate early dietary treatment in one subject. Macrocephaly was foun d in three. Computed tomography and magnetic resonance investigations in 10 showed deep bitemporal spaces in 7. Neuropsychological testing o f 8 of 12 subjects demonstrated receptive language function to be supe rior to expressive language and motor function. Cognitive functions we re obviously less affected than motor functions. A review of 57 pooled cases showed that a severe dystonic syndrome developed in 77%, a mild extrapyramidal syndrome in 10%, and 12% were asymptomatic. This disor der may pass undetected in the cerebral palsy and mentally retarded ch ild and adult populations. Repeated urine examinations of organic acid s in the urine and enzyme assay may be necessary to confirm GA-I.