Dopa-Responsive Dystonia: Symptoms, Causes, Treatments
Author: Thomas C. Weiss : Contact: Disabled World
Published: 2015-05-01 : (Rev. 2018-10-28)
Synopsis and Key Points:
Information regarding Dopamine-responsive dystonia (DRD), a genetic movement disorder which usually manifests during early childhood.
What is Dopa-Responsive Dystonia?
Dopa-Responsive Dystonia or, 'DRD,' is a hereditary form of dystonia. It is characterized by progressive difficulty with walking. DRD symptoms might be similar to those of early-onset generalized dystonia. Dopamine-responsive dystonia, (Hereditary progressive dystonia with diurnal fluctuation, Segawa's disease, or Segawa's dystonia) - A genetic movement disorder which usually manifests itself during early childhood at around ages 5 to 8 years (variable start age). Symptoms include increased muscle tone (dystonia, such as clubfoot) and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion. Children with DRD are often misdiagnosed as having cerebral palsy.
DRD classically presents as a dystonic gait disorder in a person's early childhood.
While symptoms commonly present around the age of seven, clinical observations in a number of families have made it evident that manifestations of DRD can appear at any age.
The most common complaint people with DRD have is difficulty with walking. Symptoms might seem to be minor, such as muscle cramps after exercise, or present later in a person's life in a form that more closely resembles Parkinson's disease. The features of parkinsonism that can occur include instability or lack of balance, slowness of movements, or hand tremors.
The symptoms of DRD are often worse later in the day and might increase with exertion. They are almost always better in the morning, after a person has slept.
DRD is thought to be due to abnormal functioning of the basal ganglia, which are deep brain structures involved with the control of a person's movement. The basal ganglia assist with initiating and regulating movement. Exactly what goes wrong in a person's basal ganglia remains an unknown. An imbalance of dopamine, a neurotransmitter in the basal ganglia, might underlie several different forms of dystonia, yet more research needs to be conducted for an increased understanding of the brain mechanisms involved with dystonia.
Two genes responsible 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 enzymes contribute to the production of dopamine. When these genes are affected so they are unable to fully accomplish the job of producing dopamine and the levels of dopamine in a person's body are reduced - people start to have issues with movement.
The most commonly identified form is termed,' dopa-responsive dystonia,' which is a dominantly inherited condition caused 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). Approximately 40% of people with DRD do not present a mutation in the GTP-CH1 or the hTH genes.
Other known inherited metabolic conditions may cause DRD, to include autosomal recessive deficiencies of GTP-CH1 and aromatic L-amino acid decarboxylase and additional defects of tetrahydrobiopterin metabolism. These recessively inherited conditions often times affect cognitive function, which is not associated with the dominantly inherited DRD. If; however, the symptoms of dominantly inherited DRD affect a person's speech - a cognitive issue might be presumed even though in reality the person's cognitive function is average.
Dr. Masaya Segawa from Japan first described this condition as, "hereditary progressive dystonia with marked diurnal variation." 'Dopa-Responsive Dystonia (DRD),' is the term used to describe the dystonias that respond to levodopa and is used widely in journals.
A diagnosis of DRD is not made by one single, definitive test.
Instead, it is achieved by a series of clinical observations and specific biochemical assessments. Defining the exact etiology or cause might not be possible. A therapeutic trial with levodopa is still the most practical initial approach to achieving a diagnosis of DRD. Dystonia; however, that responds to levodopa might result from multiple conditions.
Not every person with DRD responds promptly to levodopa.
Even an adverse reaction might help illuminate the etiology and prompt further testing. In addition, not all people who are carriers present with symptoms. A detailed family history is an important element of diagnosis.
Getting a cerebrospinal fluid sample through lumbar puncture is an important part of diagnosing DRD. It might be the easiest way to achieve a preliminary diagnosis and distinguish among the metabolic conditions mentioned. There is still a chance the cerebrospinal test will not provide a definitive diagnosis. It is critical that the person cease taking levodopa at least a week prior to the collection of cerebrospinal fluid. DRD also should be distinguished from other disorders with symptoms that are similar including:
- Cerebral palsy
- Spastic paraplegia
- Early-onset generalized dystonia
- Disorders that cause childhood-onset parkinsonism
A child diagnosed with early-onset generalized dystonia often times receives a trial prescription of levodopa to rule out DRD. A number of symptoms of DRD may mimic cerebral palsy (CP). Leg spasticity inhibiting a person's ability to walk happens in both disorders, yet DRD has several characteristics that set it apart from CP and other forms of neurological disorders. Most noticeable are the diurnal variation of symptoms and the hereditary aspects of DRD. CP usually results from a brain injury prior to or during birth and rarely runs in families. People and their family members should understand that diagnosing DRD can be challenging, yet these are steps toward differentiating among the various forms of dystonia that respond to lovodopa.
Treatment for dystonia is designed to help decrease the symptoms of pain, spasms, as well as functions and disturbed postures. Most therapies are symptomatic, trying to cover up or release the dystonic spasms. No one strategy will be appropriate for every person.
The symptoms of DRD can usually be treated effectively with levodopa. In many instances, full physical functionality is restored. Levodopa responsiveness has been reported to be effective in those who have been symptomatic as long as fifty years before treatment. Stable response after years of continuous treatments has been reported as well. Side-effects of the medication might include:
Support for People with DRD
Dystonia and its emotional offshoots affect every aspect of a person's life.
It affects how the person thinks, acts, as well as how they cope. By educating yourself with information, you have taken the first step towards dealing with dystonia. Stress is an inevitable part of human life and while it plainly does not cause dystonia it may aggravate dystonia symptoms. Stress-reduction programs such as meditation, relaxation techniques, or writing in a journal can be helpful.
At times, depression can be a, 'byproduct,' of dystonia.
Depression can aggravate symptoms and make them worse, but often times - treating depression may result in an improvement of dystonia. It is important to remember that depression is a disorder, it is treatable and is not a reflection of the person.
Many people are experiencing similar symptoms.
Reassurance from family members, friends, or others who have dystonia is helpful. Sharing experiences at support group meetings offers camaraderie, encouragement and the latest information regarding new treatments and medical advances.
Dopa-Responsive Dystonia Facts
- Due to commonly being misdiagnosed, it is common for the disease to remain untreated. When left untreated, patients often need achilles tendon surgery by the age of 21
- 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.
- DRD can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype. It can also occur due to de novo mutations.
- Many patients experience improvements with sleep and are relatively free of symptoms in the morning, developing increasingly severe symptoms as the day progresses.
- As this form of dystonia may be genetic, some people find it helpful to speak to a genetic counselor regarding the genetic issues and what this may mean for you and your family.
- This condition is very rare, only affecting one in two million people. It is more common in females that in males. There are several hundred cases in the United States, 25 known cases in the United Kingdom, and less than that in Australia and New Zealand.
- The estimated European prevalence of DRD ranges from 1/1,000,000-1/200,000.
- 1 - Spinal Muscular Atrophy Genetics : BioMed Central (2009/04/07)
- 2 - Foot Drop: Symptoms - Causes - Treatments : Disabled World (2015/07/09)
- 3 - Dopa-Responsive Dystonia: Symptoms, Causes, Treatments : Thomas C. Weiss (2015/05/01)
- 4 - Dystonia: Types, Causes and General Overview : Thomas C. Weiss (2015/10/28)
- 5 - Family Members, Friends, and Caring for People with Mobility Disabilities : Wendy Taormina-Weiss (2011/09/06)
- 6 - Friedreich's Ataxia: General Information and Overview : Sally Rider (2009/04/01)
- 7 - Spinal Muscular Atrophy May Also Affect the Heart : Nationwide Children's Hospital (2010/08/11)
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