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You are here: Genetic Forms > Dopa-Responsive Dystonia

What is it?
Dopa-Repsonsive Dystonia (DRD), a heredity form of dystonia, is characterised by progressive difficulty walking. Its symptoms may be similar to those of early-onset generalised dystonia.

DRD classically presents as a dystonic gait disorder in early childhood. Although symptoms usually present around age seven, clinical observations in several families have made it evident that manifestations of DRD may appear at any age. The most common complaint of people with DRD is having problems walking. 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.

DRD is believed to be due to abnormal functioning of the basal ganglia, which are deep brain structures involved with the control of movement. The basal ganglia assist in initiating and regulating movement. What goes wrong in the basal ganglia is still unknown. An imbalance of dopamine, a neurotransmitter in the basal ganglia, may underlie several different forms of dystonia, but much more research needs to be done for a better understanding of the brain mechanisms involved with dystonia.

Two genes responsive for DRD have been identified: one gene codes for the production of an enzyme called GTP cyclohydrolase and another codes for an enzyme called tyrosine hydroxylase. Both of these enzymes contribute to the production of dopamine. When these genes are affected so they can not fully accomplish the task of producing dopamine and the levels of dopamine in the body is reduced, people begin to have problems moving.

The most commonly identified form is termed dopa-responsive dystonia, which is a dominantly inherited condition cause by mutations in the GTP cyclohydrolase 1 gene (GTP-CH1). Another common form of DRD is caused by a mutation in the recessively inherited tyrosine hydroxylase gene (hTH).

About 40% of DRD patients do not present a mutation in the GTP-CH1 or the hTH genes. Other known inherited metabolic conditions may cause DRD (including 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.

Dr. Masaya Segawa of Japan first described this condition as "hereditary progressive dystonia with marked diurnal variation." Dopa-Responsive Dystonia is the term used to describe the dystonias that respond to levodopa and is used broadly in journals.

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 etiology, or cause, may not be possible.

A therapeutic trial with levodopa remains the most practical initial approach to diagnosis. However, dystonia that responds to levodopa may result from multiple conditions.

Not all DRD patients respond immediately to levodopa, and even an adverse reaction may help illuminate the etiology and warrant additional tests. 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 the metabolic conditions mentioned above. 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.

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

A child diagnosed with early-onset generalised dystonia will often receive a trial prescription of levodopa to rule out DRD.

Many symptoms of DRD may mimic cerebral palsy (CP). Leg spasticity inhibiting the ability to walk occurs in both disorders, but DRD has several characteristics that set it apart from CP and other neurological disorders. Most noticeable are the diurnal variation of symptoms and the hereditary aspects of DRD. CP usually results from a brain injury before or during birth and rarely runs in families.

Patients and family members should realize that diagnosing DRD can be challenging, but that these are steps toward differentiating among the various types of dystonia that respond to levodopa.

Treatment for dystonia is designed to help lessen the symptoms of spasms, pain, and disturbed postures and functions. Most therapies are symptomatic, attempting to cover up or release the dystonic spasms. No single strategy will be appropriate for every case.

Symptoms of DRD can usually be treated effectively with levodopa (Sinemet). In many cases, full physical functionality is restored. Levodopa responsiveness has been report to be effective in people have been symptomatic as long as 50 years prior to treatment. Stable response after years of continuous treatment has also been reported. Side effects of the medication may include light-headedness, nausea, constipation, and, in some cases, fatigue.

Dystonia and its emotional offshoots affect every aspect of a personís 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 oneís self.

Many people are experiencing similar symptoms. Reassurance from family, friends, and others who have dystonia is beneficial. Dystonia Ireland has a support group in Dublin and it is our intention eventually to set up similar groups throughout Ireland. Sharing experiences at support group meetings offers encouragement, camaraderie, and the latest information about new treatments and medical advances.

With written permission, this information is reproduced from materials published and copyrighted by the Dystonia Medical Research Foundation, Chicago, IL, USA  www.dystonia-foundation.org


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