A case of glutaric acidemia type I: Effect of riboflavin and carnitine

Glutaric acidemia, type I, is an organic acidemia associated with a progressive neurologic disorder. 1 By 1 year of age, affected individuals generally have recurrent episodes of vomiting and lethargy associated with metabolic acidosis. Progressive neurologic defici ts include dysarthria, dystonia, and choreoathetosis. Most affected Children are also mentally retarded. The presumptive diagnosis of GA-I is made by gas chromatography-mass spectrometry of urine revealing peaks of glutaric acid and its principal metabolites 3-OH-glutarate and glutaconate. The enzyme deficiency, glutaryl CoA dehydrogenase, is demonstrable in leukocytes, fibroblasts, and hepatocytes. 2 Therapeutic approaches have included low-protein diets and diets low in tryptophan and lysine, the precursors of glutaryl CoA. 3 Riboflavin (as flavin adenine dinucleotide), a cofactor of glutaryl CoA dehydrogenase, has been given to enhance residual enzyme activity? L-Carnitine has been used to stimulate the formation and excretion of shortchain acylcarnitine derivatives of glutaric acid. 4 Finally, because of evidence of inhibition of synthesis of G A B A by glutaric acid and the presence of decreased G A B A in brains of affected individuals, the G A B A analog baclofen has been given) With these techniques, progression of symptoms has been arrested in a number of cases but little clinical improvement has resulted? -8 The present report concerns a boy with GA-I who had progressive dystonic cerebral palsy associated with basal ganglia degeneration and who responded to riboflavin and L-carnitine therapy with evidence of biochemical and clinical improvement.