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Each column keeps its native condition scope. Initial features are displayed alphabetically, not ranked by clinical importance. Counts remain separate, and an empty cell does not mean a feature cannot occur.

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Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"

Mutations in the GCH1 gene are the most common cause of dopa-responsive dystonia. Less often, mutations in the TH or SPR gene cause this condition.

The GCH1 gene provides instructions for making an enzyme called GTP cyclohydrolase. This enzyme is involved in the first of three steps in the production of a molecule called tetrahydrobiopterin (BH4). The SPR gene, which provides instructions for making the sepiapterin reductase enzyme, is involved in the last step of tetrahydrobiopterin production. Tetrahydrobiopterin helps process several protein building blocks (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Specifically, tetrahydrobiopterin is involved in the production of two neurotransmitters called dopamine and serotonin. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite.

The protein produced from the TH gene is also involved in dopamine production. The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which helps convert the amino acid tyrosine to dopamine.

Mutations in the GCH1 or SPR gene impair the production of tetrahydrobiopterin, which leads to a decrease in the amount of available dopamine. TH gene mutations result in the production of a tyrosine hydroxylase enzyme with reduced function, which leads to a decrease in dopamine production. A reduction in the amount of dopamine interferes with the brain's ability to produce smooth physical movements, resulting in the dystonia, tremor, and other movement problems associated with dopa-responsive dystonia. Sleep and mood disorders also occur in some individuals with GCH1 or SPR gene mutations; these disorders likely result from a disruption in the production of serotonin. Problems with sleep and episodes of depression are not seen in people with dopa-responsive dystonia caused by TH gene mutations, which is sometimes referred to as Segawa syndrome.

Some people with dopa-responsive dystonia do not have an identified mutation in the GCH1, TH, or SPR gene. The cause of the condition in these individuals is unknown.

MedlinePlus Genetics: Causes

","key":"forms","title":"What causes Dopa-responsive dystonia?"},{"bodyHtml":"

Signs and symptoms of dopa-responsive dystonia usually appear during childhood, most commonly around age 6. The first signs of the condition are typically the development of inward- and upward-turning feet (clubfeet) and dystonia in the lower limbs. The dystonia spreads to the upper limbs over time; beginning in adolescence, the whole body is typically involved. Affected individuals may have unusual limb positioning and a lack of coordination when walking or running. Some people with this condition have sleep problems or episodes of depression more frequently than would normally be expected.

Over time, affected individuals often develop a group of movement abnormalities called parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, tremors, and an inability to hold the body upright and balanced (postural instability).

The movement difficulties associated with dopa-responsive dystonia usually worsen with age but stabilize around age 30. A characteristic feature of dopa-responsive dystonia is worsening of movement problems later in the day and an improvement of symptoms in the morning, after sleep (diurnal fluctuation).

Rarely, the movement problems associated with dopa-responsive dystonia do not appear until adulthood. In these adult-onset cases, parkinsonism usually develops before dystonia, and movement problems are slow to worsen and do not show diurnal fluctuations.

Source: MedlinePlus Genetics

Sepiapterin reductase deficiency

Sepiapterin reductase deficiency is a condition characterized by movement problems, most often a pattern of involuntary, sustained muscle contractions known as dystonia. Other movement problems can include muscle stiffness (spasticity), tremors, problems with coordination and balance (ataxia), and involuntary jerking movements (chorea). People with sepiapterin reductase deficiency can experience episodes called oculogyric crises. These episodes involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck. Movement abnormalities are often worse late in the day. Most affected individuals have delayed development of motor skills such as sitting and crawling, and they typically are not able to walk unassisted. The problems with movement tend to worsen over time.

People with sepiapterin reductase deficiency may have additional signs and symptoms including an unusually small head size (microcephaly), intellectual disability, seizures, excessive sleeping, and mood swings.

Causes

Mutations in the SPR gene cause sepiapterin reductase deficiency. The SPR gene provides instructions for making the sepiapterin reductase enzyme. This enzyme is involved in the production of a molecule called tetrahydrobiopterin (also known as BH4). Specifically, sepiapterin reductase is responsible for the last step in the production of tetrahydrobiopterin. Tetrahydrobiopterin helps process several building blocks of proteins (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.

SPR gene mutations disrupt the production of sepiapterin reductase. Most SPR gene mutations result in an enzyme with little or no function. A nonfunctional sepiapterin reductase leads to a lack of tetrahydrobiopterin. In most parts of the body, there are alternate pathways that do not use sepiapterin reductase for the production of tetrahydrobiopterin, but these pathways are not found in the brain. Therefore, people with sepiapterin reductase deficiency have a lack of tetrahydrobiopterin in the brain. When no tetrahydrobiopterin is produced in the brain, production of dopamine and serotonin is greatly reduced. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite. The lack of these two neurotransmitters causes the problems with movement and other features of sepiapterin reductase deficiency.

MedlinePlus Genetics: Causes

MedlinePlus: Sepiapterin reductase deficiency

","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"dopa-responsive-dystonia","sourceDocuments":[{"name":"Dopa-responsive dystonia","reviewed":"2012-05","sections":{"causes":{"fetchedAt":"2026-10-20T20:21:03.200448+00:00","label":"Causes","pageSha256":"497fbded14608236980b5f39dc976f5770d90f2a63bbe13857334c24cf033fa2","sourceUrl":"https://medlineplus.gov/genetics/condition/dopa-responsive-dystonia/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/dopa-responsive-dystonia"},{"name":"Sepiapterin reductase deficiency","reviewed":"2011-06","sections":{"causes":{"fetchedAt":"2026-10-20T20:24:55.198303+00:00","label":"Causes","pageSha256":"19230792eb55c82d1dd1cda0715b070fa5d42cf9a44f2e1ac4ca47a3c954eeec","sourceUrl":"https://medlineplus.gov/genetics/condition/sepiapterin-reductase-deficiency/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/sepiapterin-reductase-deficiency"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. Feature values below retain their original sources and patient groups.","title":"Dopa-responsive dystonia"},"schemaVersion":1}