Dopa-Responsive Dystonia

Dopa-responsive dystonia (DRD) is an umbrella term used to describe specific dystonia disorders that respond to a medication called levodopa, which is a synthetic form of a brain chemical called dopamine. This group includes inherited forms that are characterized by progressive difficulty walking. Its symptoms may be similar to those of early onset generalized dystonia.

Terms used to describe dopa-responsive dystonia include DRD, Segawa’s dystonia, Segawa’s disease, DYT5 dystonia.

Symptoms

(Dopa-Responsive Dystonia) typically presents as a dystonic gait disorder beginning in early childhood. The symptoms of DRD may be similar to those of other inherited childhood onset dystonias, and begin in the legs. Symptoms may appear minor (such as muscle cramps after exercise) or present later in life in a form that more closely resembles Parkinson's disease. The features of parkinsonism that may occur include slowness of movements, instability or lack of balance, and, less commonly, tremor of the hands at rest.

Symptoms of DRD are often worse later in the day (this phenomenon is called diurnal fluctuation) and may increase with exertion.

Cause

The most commonly identified form of dopa-responsive dystonia (DRD) is sometimes referred to as Segawa's disease or DYT5 dystonia. DYT5 dystonia is a dominantly inherited condition caused by mutations in the GTP cyclohydrolase 1 gene (GTP-CH1). (A dominantly inherited disorder means that only one parent need have the gene mutation in order for a child to inherit the disorder.) This gene plays a role in the production of dopamine. When this gene is impaired and cannot fully accomplish the task of producing dopamine, the levels of dopamine in the body are compromised and a person will begin to have problems with movement.

About 40% of DRD patients do not carry the mutation in the GTP-CH1 gene associated with DYT5 dystonia. Other known inherited metabolic conditions may cause DRD (including a mutation in the recessively inherited tyrosine hydroxylase gene (hTH), autosomal recessive deficiencies of GTP-CH1 and aromatic L-amino acid decarboxylase, and other defects of tetrahydrobiopterin metabolism). These recessively inherited conditions often affect cognitive function, which is not associated with the dominantly inherited DRD. However, if the symptoms of dominantly inherited DRD affect a patient's speech, a cognitive problem may be presumed even though, in reality, the individual's cognitive function is normal.

Diagnosis

The diagnosis of dopa-responsive dystonia (DRD) is not made by one definitive test, but by a series of clinical observations and specific biochemical assessments. Defining the exact cause may not be possible.

A therapeutic trial with levodopa remains the most practical initial approach to diagnosis. Even an adverse reaction may help illuminate details about the cause and warrant additional tests, and not all DRD patients respond to levodopa immediately. Furthermore, not all individuals who are carriers will exhibit symptoms. A detailed family history is an important element of diagnosis.

Obtaining a cerebrospinal fluid sample (via lumbar puncture) is an important component of diagnosing DRD. This may be the most straightforward way to obtain a preliminary diagnosis and distinguish among possible metabolic conditions. There remains a chance that the cerebrospinal test will not provide a definitive diagnosis. It is crucial that the patient stop taking levodopa at least a week before the cerebrospinal fluid collection.

Specific metabolic defects may be detected by an oral phenylalanine loading test, but the test is not 100% sensitive and the scope is limited. False negatives may occur with this test, detecting only about 80% of cases of DRD. Similarly, there are tests for very specific metabolic conditions that do not address the entire scope of possible deficiencies.

DRD must be distinguished from other disorders with similar symptoms including cerebral palsy, early-onset generalized dystonia, spastic paraplegia, and disorders which cause childhood-onset parkinsonism.

Patients and family members should understand that diagnosing DRD can be challenging, but that there are steps toward differentiating among the various types.

Treatment

Symptoms of dopa-responsive dystonia (DRD) can usually be treated effectively with an oral medication called levodopa, and most often a combination of levodopa and carbidopa. In many cases, full physical functionality--including walking, running, speaking, writing--is restored or preserved.

Individuals with dystonia frequently experience co-existing depression and anxiety disorders. Evaluation and treatment for possible mental health disorders may be an important part of a comprehensive treatment plan.

What Type of Doctor Treats Dopa-Responsive Dystonia?

The type of doctor that is typically trained to diagnose and treat dopa-responsive dystonia is a neurologist with special training in movement disorders, often called a movement disorder specialist.

Living with Dopa-Responsive Dystonia

Living well with dopa-responsive dystonia is possible. The early stages of onset, diagnosis, and seeking effective treatment are often the most challenging.  Treatment can often dramatically control physical movement symptoms.

Individuals living with dopa-responsive dystonia are strongly encouraged to:

  • Seek out the best medical care
  • Learn about dystonia and treatment options
  • Develop a multi-layered support system of support groups, online resources, friends, and family
  • Seek expert mental health professionals to diagnose and treat possible co-existing depression or anxiety disorders
  • Investigate complementary therapies
  • Get active within the dystonia community

Last updated: September 2021

Thank you to Dystonia Medical Research Foundation (USA) for allowing us to share this information. The DMRF is a 501(c)(3) non-profit organization dedicated to advancing research for improved dystonia treatments and ultimately a cure, promoting awareness, and supporting the well-being of affected individuals and families.