Characteristic symptoms are increased muscle tone (dystonia, such as clubfoot) and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion.
Yet some people with dopamine-responsive dystonia do not experience such diurnal fluctuations, causing many researchers to prefer other disease terms.
A mutation in the gene GCH1, which encodes the enzyme GTP cyclohydrolase I, disrupts the production of BH4, decreasing dopamine levels (hypodopaminergia).
The diagnosis of dopamine-responsive dystonia can be made from a typical history, a trial of dopamine medications, and genetic testing.
Not all patients show mutations in the GCH1 gene (GTP cyclohydrolase I), which makes genetic testing imperfect.
Sometimes a lumbar puncture is performed to measure concentrations of biopterin and neopterin, which can help determine the exact form of dopamine-responsive movement disorder: early onset parkinsonism (reduced biopterin and normal neopterin), GTP cyclohydrolase I deficiency (both decreased) and tyrosine hydroxylase deficiency (both normal).
An MRI scan of the brain can be used to look for conditions that can mimic dopamine-responsive dystonia (for example, metal deposition in the basal ganglia can indicate Wilson's disease or pantothenate kinase-associated neurodegeneration).
In those with dopamine-responsive dystonia, symptoms typically dramatically improve with low-dose administration of levodopa, which is a biochemically significant metabolite of the amino acid phenylalanine, as well as a biological precursor of the catecholamine dopamine, a neurotransmitter.
In addition, the effectiveness of such therapy is typically long term, without the complications that often occur for those with Parkinson's disease who undergo L-dopa treatment.
The disease less commonly begins during puberty or after age 20, and very rarely, cases in older adults have been reported.
To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders.