Dopa-Responsive

Dopa-Responsive

What is it?
Dopa-Repsonsive Dystonia (DRD), is a broad term used to describe forms of dystonia that respond to a medication called levodopa(Sinemet) which is a synthetic form of a brain chemical called dopamine. This group includes hereditary forms that are  characterised by progressive difficulty in walking. Its symptoms may be similar to those of early-onset generalised.

 

Terms used to describe dopa-responsive dystonia include:

DRD, Segawa’s dystonia, Segawa’s disease, DYT 5 dystonia

 

Symptoms
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 generalised 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 (diurnal fluctuation) and may increase with exertion. They are almost always better in the morning after sleep.

 

Cause

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 the 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 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  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 patient’s cognitive function is normal.

 

Diagnosis
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 hep illuminate details about the cause and warrant additional tests, and not all DRD patient’s 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 easiest 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 generalised dystonia, spastic paraplegia, and disorders which cause childhood-onset parkinsonism.

 

Patient’s and family members should understand that diagnosing DRD can be challenging, but that there are steps toward differentiating among the various types of dystonia that respond to levodopa.

 

Treatment

Symptoms of DRD can usually be treated effectively with a drug called levodopa and carbidopa. In many cases, full physical functionality including walking, running, speaking and writing is restored or preserved.

 

Support
Dystonia and its emotional offshoots affect every aspect of a person’s life – how we think, the way we act, and how we cope. By educating yourself with information, you have taken the first step in dealing with dystonia.

 

Stress is an inevitable part of life, and although it clearly does not cause dystonia, it can aggravate dystonia symptoms. Stress-reduction programmes such as relaxation techniques, meditation, and journal writing may be beneficial.

 

Sometimes depression can be a byproduct of dystonia. Depression may aggravate symptoms and make them worse, but, often, treating depression can result in an improvement of dystonia. It is important to remember that depression is a disorder; it is treatable and not a reflection of one’s self.

 

Many people are experiencing similar symptoms. Reassurance from family, friends, and others who have dystonia is beneficial. Sharing experiences at support group meetings offers encouragement, camaraderie, and the latest information about new treatments and medical advances.

 

Dystonia Ireland gratefully acknowledges  the Dystonia Medical Research Foundation for use of this information.