Dopa-responsive dystonia is a genetically heterogeneous syndrome that typically presents in children as leg dystonia and parkinsonism. Similar to juvenile-onset Parkinson disease, dopa-responsive dystonia is due to dopamine depletion, but unlike Parkinson disease, dopamine deficiency arises secondary to a defect in neurotransmitter synthesis rather than a loss of dopaminergic neurons. In this article, the author reviews the cardinal features, diagnosis, pathophysiology, treatment, and differential diagnosis of dopa-responsive dystonia, including related disorders of neurotransmitter metabolism.
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• Dopa-responsive dystonia is a syndrome that typically presents in children as leg dystonia and parkinsonism.
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• Dopa-responsive dystonia is a genetically heterogeneous disorder that can be inherited in either an autosomal dominant or autosomal recessive fashion.
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• The most common pattern of dopa-responsive dystonia inheritance is autosomal dominant, and the majority of affected families have a mutation in the (GTP cyclohydrolase1) gene, GCH1.
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• Dopa-responsive dystonia responds dramatically to low-dose levodopa therapy, independent of patient age or disease duration.
Historical note and terminology
The first description of dystonia specifically responsive to levodopa was provided in 1971 by Segawa (131). In the midst of the excitement of Parkinson disease treatment with levodopa, Segawa reported several young girls with prominent diurnal variation of dystonia whose symptoms were ameliorated with low-dose levodopa (128). Subsequent reports described families whose members had dystonia and parkinsonism that improved markedly following levodopa treatment. Further studies have distinguished dopa-responsive dystonia from young-onset Parkinson disease with dystonia and have clarified the genetic basis of the disorder (100; 106). Among the inherited forms of secondary dystonia, dopa-responsive dystonia or hereditary progressive dystonia with diurnal variation (HPD) is classified as DYT5, a “dystonia-plus syndrome,” because of its association with other neurologic features (ie, parkinsonism), although evidence of neurodegeneration is lacking (31; 40).