Dopa-responsive dystonia (DRD) is a broad term used to describe forms of dystonia that respond to a medication called levodopa, which is a synthetic form of a brain chemical called dopamine. This group includes heredity 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
DRD typically presents as a dystonic gait disorder that begins in early childhood. The symptoms of DRD may be similar to those of early-onset generalized dystonia, 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.
The most commonly identified form of dopa-responsive dystonia is sometimes referred to as 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.
The diagnosis of 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.
Symptoms of DRD can usually be treated effectively with a drug 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.