The following information may help to address your question:
What is dopa-responsive dystonia?
(DRD) is an inherited
type of dystonia
that typically begins during childhood but may begin in adolescence or adulthood.
Depending on the specific type of DRD, specific symptoms can vary. Features can range from mild to severe. In most cases, dystonia begins in the lower limbs and spreads to the upper limbs over time. Symptoms may include unusual limb positioning; a lack of coordination when walking or running; sleep problems; and episodes of depression. Affected people also often develop a group of movement abnormalities called parkinsonism
. Although movement difficulties usually worsen with age, they often stabilize around age 30. DRD may be caused by mutations
in the GCH1, TH
or SPR genes
, or the cause may be unknown. Depending on the genetic cause, DRD may be inherited in an autosomal dominant
(most commonly) or autosomal recessive
manner. This form of dystonia is called 'dopa-responsive' dystonia because the symptoms typically improve during treatment with levodopa and carbidopa
Last updated: 4/30/2015
What are the signs and symptoms of dopa-responsive dystonia?
The most common form of dopa-responsive dystonia (DRD) is autosomal dominant DRD
(caused by a mutation in the GCH1
gene). This form of DRD is usually characterized by childhood-onset dystonia that may be associated with parkinsonism
at an older age. The average age of onset is 6 years, and females are 2-4 times more likely than males to be affected. Symptoms usually begin with lower limb dystonia, resulting in gait problems that can cause stumbling and falling. Symptoms are often worse later in the day, a phenomenon known as diurnal fluctuation. In rare cases, the first symptom may be arm dystonia, tremor of the hands, slowness of movements, or cervical dystonia. This form of DRD usually progresses to affect the whole body, and some people also develop parkinsonism. Depression, anxiety, sleep disturbances and obsessive-compulsive disorder have been reported in some people. Intellectual function is normal. Those with onset at older ages tend to be more mildly affected.
Another form of DRD is due to a rare condition called sepiapterin reductase deficiency
, which is inherited in an autosomal recessive
manner. This form of DRD is also characterized by dystonia with diurnal fluctuations, but also affects motor and cognitive development. Onset usually occurs before the first year of life. Sleep disturbances and psychological symptoms (anxiety, irritability) are common later in childhood.
A third form of DRD is autosomal recessive DRD, also called tyrosine hydroxylase deficiency
. This form is characterized by a spectrum of symptoms, ranging from those seen in the autosomal dominant form to progressive infantile encephalopathy
. Onset is usually in infancy. Intellectual disability
, developmental motor delay, and various other features may be present.
Last updated: 5/1/2015
How is dopa-responsive dystonia diagnosed?
Dopa-responsive dystonia (DRD) is diagnosed based on the signs and symptoms present, results of laboratory tests (sometimes including genetic testing
), and response to therapy with levodopa
If DRD is suspected, a therapeutic trial with low doses of levodopa remains the most practical approach to the diagnosis. It is generally agreed that people with childhood-onset dystonia of unknown cause should be treated initially with levodopa. The characteristic symptoms and response to treatment are sufficient to establish the diagnosis for people with the most common form, autosomal dominant DRD
. There is only one gene in which mutations are known to cause this form of DRD, but not all people with the disorder are found to have a mutation in the responsible gene. While finding a mutation may provide information about prognosis
, it does not alter the treatment. Other types of laboratory tests, such as measuring specific substances or enzymes
in the blood or cerebrospinal fluid (CSF), may be useful to support the diagnosis.
For tyrosine hydroxylase deficiency
, an autosomal recessive genetic cause of DRD, molecular genetic testing has confirmed the presence of mutations in all affected people to date. Specific laboratory tests performed on CSF help support the diagnosis but are not diagnostic on their own.
For sepiapterin reductase deficiency
, a very rare autosomal recessive form of DRD, there are distinctive findings in CSF and reduced or absent activity of sepiapterin reductase in fibroblasts
. Molecular genetic testing can identify mutations in the responsible gene and confirm the diagnosis of this form of DRD.
The major conditions that may have a similar presentation to DRD and are part of the differential diagnosis
include early-onset parkinsonism
, early-onset primary dystonia
, and cerebral palsy
or spastic paraplegia
People with specific questions about being evaluated for any form of dystonia should speak with a neurologist
or other health care provider.
Last updated: 5/1/2015
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