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Dopa-responsive dystonia (DRD) typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It may also present with a ``cerebral-palsy`` like picture with onset in infancy, or more rarely as a focal dystonia with onset typically in adulthood or even as parkinsonism in adulthood. The estimated prevalence in the general population of Europe is between 1 and 5 per million. The disease is inherited in an autosomal dominant or recessive manner. The classical biochemical defect is a deficiency of tetrahydrobiopterin (BH4). This led to the discovery of causative mutations for DRD in the GTP-cyclohydrolase I gene (GCH-1) on chromosome 14q. GCH-1 is the rate limiting enzyme in the synthesis of BH4. Mutations in the tyrosine hydroxylase gene and Parkin gene can also lead to a similar phenotype. Unlike all other forms of dystonia, DRD is an eminently treatable condition. Many patients already notice a dramatic improvement after the first small dose of L-Dopa. However, some patients need to be on L-Dopa treatment for a considerably longer time before improvement can definitely be noticed. Adult patients with suspected DRD should be prescribed a total daily dose of 300-400 mg L-Dopa (combined with a peripheral decarboxylase inhibitor) for four weeks, the dose should then be increased to 600 mg for the subsequent four weeks. |