Severe dystonic encephalopathy without hyperphenylalaninemia associated with an 18-bp deletion within the proximal GCH1 promoter.

In a recent GCH1 mutation screen, an 18-bp deletion was identified within the proximal promoter in two patients with early-onset Parkinson's disease. The mutation removes cAMP response element critical for adequate GTP cyclohydrolase I activity in selected cell types, including dopaminergic neurons, but its biological significance was unclear as it was also detected in one control individual. We present an 11-year-old boy with infantile-onset severe dystonic encephalopathy without hyperphenylalaninemia whom we found compound heterozygous for the same promoter GCH1 deletion and another common missense mutation associated with classical dopa-responsive dystonia. Extensive diagnostic work up excluded other causes of dystonia, and comprehensive mutation scan did not reveal any additional GCH1 sequence variations, supporting the association between the promoter deletion and disease phenotype.