Wilson’s Disease
Very effective treatments are available for a few rare disorders where dystonia may be a presenting or dominating feature on examination.[20-22] Wilson’s disease is the prototype example. It is a disorder of copper metabolism. Approximately 85% of patients have some form of dystonia, often combined with Parkinsonism, tremor, or other neurological features. Copper chelation therapy can prevent progression and even reverse disability. Because Wilson’s disease has a fatally progressive course without treatment, it should be excluded with appropriate diagnostic testing in every child and young adult with dystonia. A low serum ceruloplasmin and a slit lamp exam by an ophthalmologist specifically looking for the presence of Kaiser-Fleischer rings provide useful screening tests. This may be followed by urinary tests of copper excretion and/or liver biopsy if diagnostic uncertainty remains.
Dopa-Responsive Dystonia
Dopa-responsive dystonia presents in children and young adults as a relatively isolated dystonia but it often is combined with Parkinsonism. Corticospinal features are reported for some cases, such as spasticity and brisk reflexes. Although dopa-responsive dystonia constitutes only a small fraction of all childhood dystonias, a trial of levodopa is warranted in all children and young adults with dystonia because of its dramatic and sustained efficacy.[23] A dramatic and sustained response can be considered diagnostic. Among those who respond to levodopa, the role for confirming the diagnosis via lumbar puncture to identify low CSF biopterin levels remains unclear. There are simple genetic tests for the most common forms of dopa-responsive dystonia associated with mutations of the GCH1 or TH genes, but sensitivity is not 100% for detecting all mutations.
Other Treatments
As ongoing research reveals additional causes for dystonia, the numbers of disorders with specific mechanism-based treatments has continued to grow. Guidelines for which disorders to consider and what tests to employ vary among different centers. The following disorders should be considered in the appropriate clinical setting. Biotin-responsive basal ganglia disease is a very rare condition that may present with prominent dystonia in children or young adults, often in combination with other neurological signs including Parkinsonism, ocular motility defects, and episodes of encephalopathy.[24-26] An important clue is peculiar signal changes in the caudate and putamen on MRI. Symptoms can be reversed with biotin supplements; death ensues if the disorder untreated.
Vitamin E deficiency is dominated by ataxia with neuropathy, but dystonia may be a presenting feature and may predominate in later stages.[27-29] Serum vitamin E levels are useful for diagnosis, and treatment involves dietary supplements. Deficiency of the glucose transporter, GLUT1, due to mutations in the SLC2A gene classically presents with psychomotor delay, seizures, and a mixed motor disorder. A more recently recognized phenotype of GLUT1 deficiency is paroxysmal exercise-induced dystonia. The diagnosis can be made via genetic testing and effective treatment requires a ketogenic diet.
Table 2: Treatable Disorders with Dystonia
Disorder |
Typical age of onset
|
Typical clinical features
|
Associated laboratory features |
Treatment
|
|
Biotin-responsive basal ganglia disease
|
children through young adults
|
acute encephalopathy, generalized dystonia, Parkinsonism, quadriparesis
|
brain MRI shows abnormal signal in caudate and sometimes putamen
|
biotin supplements reverse disorder
|
|
Dopa-responsive dystonia
|
children through young adults
|
generalized dystonia, often Parkinsonism, sometimes spasticity
|
low CSF biopterins, abnormal gene test
|
levodopa reverses disability
|
|
GLUT1 deficiency
|
children through young adults
|
paroxysmal dystonia
|
low CSF glucose
|
ketogenic diet reduces attacks
|
|
Vitamin E deficiency
|
children through young adults
|
generalized dystonia, often with ataxia and neuropathy
|
low serum vitamin E
|
Vitamin E supplements may retard progression
|
|
Wilson’s disease
|
children through young adults
|
generalized dystonia, often Parkinsonism, hepatopathy
|
low serum ceruloplasmin, high urinary copper
|
copper chelation can reverse disability and prevent progression
|
H. A. Jinnah, MD PhD
Emory University School of Medicine
Atlanta, GA 30307