The exact prevalence of DRD is not well established. The estimated prevalence of DRD in Europe ranges from 1 in 1,000,000 to 1 in 200,000 people, but it is likely underdiagnosed due to mild cases or similarities to other forms of dystonia.

DRD is primarily caused by genetic mutations affecting dopamine synthesis. These mutations lead to reduced dopamine production, and since dopamine allows the brain to direct smooth physical movements, a lack of it interferes with smooth muscle control and the characteristic symptoms of the disorder. The most common mutations include those of the following genes:

• GCH1 gene for the enzyme GTP cyclohydrolase 1 inherited in an autosomal dominant pattern (see RareShare Guide on Genetic Inheritance);  this is the most common cause.

• TH gene for tyrosine hydroxylase inherited in an autosomal recessive pattern.

• SPR gene for sepiapterin reductase inherited in an autosomal recessive pattern.

Symptoms of DRD typically emerge in childhood around age 6 or adolescence and often worsen with age but stabilize around age 30. Symptoms range from mild to severe and may include:

• Dystonia (involuntary muscle contractions, often starting in the lower limbs)

• Bradykinesia (slowness of movement)

• Diurnal fluctuation (symptoms often worsen throughout the day and improve after rest)

• Abnormal postures and gait (e.g., toe walking)

• Other movement abnormalities (e.g., tremors, rigidity)

• Cognitive and psychiatric symptoms in some cases, such as anxiety, depression, sleep disturbances and obsessive-compulsive behaviors.

• Parkinsonism: after developing symptoms over a long period of time, an individual with DRD can develop this group of abnormalities including unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability)

Diagnosis of DRD involves a comprehensive clinical evaluation, including:

• Medical history and symptom assessment (such as childhood-onset dystonia with diurnal fluctuations).

• Neurological examination.

• Genetic Testing: Identification of mutations in the GCH1, TH or SPR genes can confirm the diagnosis.

• Biochemical Tests: Cerebrospinal fluid (CSF) analysis to assess neurotransmitter levels; phenylalanine loading test.

• Brain MRI (usually normal in DRD).

• Response to Levodopa (L-DOPA): A positive response to dopaminergic treatment is a hallmark of DRD and can help confirm the diagnosis.

The primary treatment for DRD is dopaminergic drug and physical therapy:

• Levodopa (L-DOPA): a precursor molecule to dopamine often used to treat people with Parkinson’s disease. Often combined with carbidopa to enhance effectiveness and reduce side effects.

• Bromocriptine: A dopamine agonist sometimes used as an alternative or adjunct to levodopa.

• Physical Therapy: To assist in managing symptoms and improving mobility.

• Botulinum Toxin Injections: Can be used for focal dystonia in certain cases.

Patients generally experience significant symptom improvement once drug treatment is initiated. Early diagnosis and treatment are crucial, as untreated patients may become wheelchair-bound. However, even after years of delayed treatment, patients often show complete symptom resolution with L-DOPA therapy. Lifelong treatment is typically required

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2. Jankovic, J., & Tan, E. K. (2010). "Dystonia: Causes and management." The Lancet Neurology, 9(11), 1106-1118.

3. Nutt, J. G., & Woodward, W. R. (2018). "Diagnosis and treatment of dopa-responsive dystonia." Cleveland Clinic Journal of Medicine, 85(4), 295-302.

4. Ghosh, P. S., & Koller, W. C. (2020). "Genetics of dystonia: An overview." Movement Disorders Clinical Practice, 7(3), 233-245.

5. Wijemanne, S., & Jankovic, J. (2015). “Dopa-responsive dystonia—clinical and genetic heterogeneity.” Nature Reviews Neurology, 11(7), 414-424.

6. Orphanet:  Dopa-responsive Dystonia.

7. Medline:  https://medlineplus.gov/genetics/condition/dopa-responsive-dystonia/ 

8. National Library of Medicine:  https://www.ncbi.nlm.nih.gov/books/NBK482140/