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J
im Black, MD, of the University of
Birmingham, UK, explained that
dopa-responsive dystonia is a child-
hood-onset dystonic disorder (onset
usually age 5–8 years) characterized
by a dramatic response to low doses of
levodopa.
Dopa-responsive dystonia is very rare,
affecting one in two million individuals.
It is more common in females than in
males. Several hundred cases are in the
US, 25 known cases in the UK, and fewer
in Australia and New Zealand.
Characteristic symptoms are increased
muscle tone and Parkinsonian features,
typically absent in the morning or after
rest but worsening during the day and
with exertion. Owing to the rarity of the
disease, children with dopa-responsive
dystonia are often misdiagnosed as
suffering with cerebral palsy. This mis-
diagnosis results in patients often living
their entire childhood with the condition
untreated.
When left untreated, patients often need
Achilles tendon surgery by age 21 years.
They will also struggle with walking, which
degrades throughout the day. Power
napping can provide temporary relief in
untreated patients.
Improvement with sleep, with relative
freedom from symptoms in the morning,
and increasingly severe symptoms as the
day progresses has led to the disorder
being referred to as progressive heredi-
tary dystonia with diurnal fluctuations. Yet
NoMutations in the Three Genes
Involved in BH4 Biosynthesis and
Recycling were Identified in a Cohort
of Patients with Dopa-Responsive
Dystonia
No mutations in the three genes involved in tetrahydrobiopterin (BH4) biosynthesis and
recycling were identified in a cohort of patients with dopa-responsive dystonia.
not all patients experience such diurnal
fluctuations, causing many researchers to
prefer other terms for the disease.
Dopa-responsive dystonia also impairs
development into adulthood, reduces
balance, and reduces calf muscle
development. Socially, it can result in
depression, lack of social skills, and ina-
bility to find employment.
The diagnosis of dopa-responsive dys-
tonia can be made from a typical history,
a trial of dopamine medications, and
genetic testing. Not all patients show
mutations in the GCH1 gene (GTP cyclohy-
drolase I), which renders genetic testing
imperfect.
Lumbar puncture is sometimes performed
to measure concentrations of biopterin
and neopterin, which can help determine
the exact form of dopamine-responsive
movement disorder. Forms are early onset
parkinsonism (reduced biopterin and
normal neopterin), GTP cyclohydrolase I
deficiency (both decreased), and tyrosine
hydroxylase deficiency (both normal).
In approximately half of cases, a phenyla-
lanine loading test can be used to show
decreased conversion from the amino
acid phenylalanine to tyrosine. This pro-
cess uses BH4 as a cofactor.
Decreased twitching may be noticed
during REM sleep during a sleep study.
Brain MRI scanning can be used to look
for conditions that can mimic dopa-
responsive dystonia. For example, metal
deposition in the basal ganglia can
indicate Wilson’s disease or pantothenate
kinase-associated neurodegeneration.
Nuclear imaging of the brain using
position emission tomography (PET
scanning) shows normal radiolabeled
dopamine uptake in dopa-responsive
dystonia, contrary to the decreased
uptake of Parkinson's disease.
Other differential diagnoses include:
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