Disease Process: Dopa-Responsive Dystonia

Disease Process: Dopa-Responsive Dystonia

Jessica Clark

Liberty University

BIOL 102

Author Note

Jessica Clark, Liberty University, BIOL 102, Disease Process: Dopa-Responsive Dystonia

Disease Process: Dopa-Responsive Dystonia

 According to Albanese et al., (2013), “dopamine-responsive dystonia (aka. dopa-responsive dystonia) is an autosomal dominant neurologic disorder characterized by incomplete penetrance and high variability of its phenotypic expression”. This neurological disorder primarily affects the skeletal system, muscular system, and nervous system. Dopa-responsive dystonia is a hereditary progressive dystonia with diurnal fluctuation (Patient registry, n.d.). It is a genetic movement disorder which usually develops during early childhood but can [rarely] develop during adulthood. Adult symptoms are displayed in appearance like that of Parkinson’s Disease. However, unlike Parkinson’s Disease, DRD is not a neurodegenerative disease.  

Description

Symptoms of dopa-responsive dystonia typically present themselves in patients at around age 6 with the first signs of the disorder being dystonia of the lower limbs (Schiller, Wevers, Steenbergen, Blau & Jung, 2004). If left untreated, the dystonia typically spreads to the upper portion of the body, affecting the extremities, torso, and in some cases the neck (Albanese et al., 2013). Eventually, the condition plateaus at around age 30, leaving the entire body affected by movement abnormalities which present as dystonic movements and parkinsonian features – also know as parkinsonism (Asmus F., Gasser T., 2010).  

According to the U.S. Department of Health & Human Services’ National Library of Medicine, dopa-responsive dystonia, also known as L-dopa dystonia, is a condition that affects the muscular system by causing involuntary muscle contractions, tremors, and other uncontrolled movements (dystonia) (Genetics Home Reference, 2019). Bodily functions affected by dopa-responsive dystonia have been found in recent years to be caused by an abnormality in the basal ganglia region of the brain. This malfunction of the basal ganglia is thought to be caused by an imbalance of the neurotransmitter dopamine. As a result, this imbalance causes the skeletal and muscular system to overreact, causing sustained involuntary movements that are often painful.

Diagnosis

According to genetic experts, “Dopa-responsive dystonia is diagnosed based on the signs and symptoms present, results of laboratory tests (sometimes including genetic testing), and response to therapy with levodopa” (Nikhar N., 2014). As a result of dopamine-responsive dystonia being such a rarity, this condition tends to often be misdiagnosed as another condition with similar symptoms. When it is accurately diagnosed, the normal testing procedures may include, compiling and reviewing the family medical history of the patient, genetic testing, PET scan, MRI, and administering a trial of levodopa medications.

 Moreover, the diagnosis process will always include a review of the patient’s symptoms. Patients presenting with dopamine-responsive dystonia symptoms share a list of common features, including, abnormal gait, hand tremor, dystonic movements that worsen with stress and fatigue, and (as found in adult patients) parkinsonian features.  Further, the main cause of dopa-responsive dystonia is due to a mutation found among several genes. One of the genes affected by this mutation is found in gene GCH1. This mutation found in gene GCH1 (which encodes the enzyme GTP cyclohydrolase 1) is responsible for the disruption of the production of BH4, which, consequently, reduces dopamine levels and manifests its side effects as dystonic movements and parkinsonian features ("OMIM Entry - # 128230 - dystonia; dopamine-responsive dystonia ", 2019).

Treatment

As found among correctly diagnosed patients suffering from dopa-responsive dystonia, a treatment of low-dose levodopa has proven to dramatically improve symptoms.  With regular use, levodopa therapy has demonstrated a sustained pattern of relief from symptoms. Although levodopa therapy offers patients an avenue of relief from symptoms, due to common misdiagnosis of patients (specifically adult-onset patients) with dopamine-responsive dystonia, many have been left without successful treatment (Gordon, 2007).  Moreover, with the presentation of dopamine-responsive dystonia symptoms being a result of a genetic mutation, prevention of this painful condition cannot currently be made possible.

One of the more recent methods of treatment being utilized by dopamine-responsive dystonia sufferers is the use of botulinum toxin injections (aka. Botox) (Kojovic, et al., 2011). According to Kojovic (2011), “Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions”. By injecting Botox into specific muscles, contractions and abnormal postures are shown to improve when repeated on a quarterly basis.

In addition to these other forms of treatment, physical therapy, speech therapy, specific stretching techniques, and getting massages to relieve muscle pain, have also proven to be helpful. As a last resort, after first trying these other alternatives, surgery is an option for patients suffering severe symptoms. Deep brain stimulation surgery has become increasingly popular during recent years for qualifying dopamine-responsive dystonia candidates. According to Mayo Clinic (2019), “Electrodes are surgically implanted into a specific part of your brain and connected to a generator implanted in your chest. The generator sends electrical pulses to your brain that might help to control your muscle contractions. The settings on the generator can be adjusted to treat your specific condition”.

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