Levodopa‐induced dyskinesias in tyrosine hydroxylase deficiency

Abstract

The objective of this study was to characterize levodopa (l-dopa)-induced dyskinesias in patients with tyrosine hydroxylase deficiency. Clinical observation was carried out on 6 patients who were diagnosed with tyrosine hydroxylase deficiency and were treated with escalating doses of l-dopa. All 6 patients showed l-dopa-induced dyskinesias of variable intensity early in the course of treatment and regardless of the age of initiation. l-Dopa-induced dyskinesias were precipitated by increases in the dose of l-dopa and also by febrile illnesses and stress. They caused dysfunction and distress in 2 patients. The dyskinesias were improved by decreasing the l-dopa dose or by slowing its titration upward. Increasing the dose frequency was helpful in 2 patients, and introducing amantadine was helpful in another 2 patients. l-Dopa-induced dyskinesias are a common phenomenon in tyrosine hydroxylase deficiency. The current observations show that l-dopa-induced dyskinesias are frequent in a dopamine-deficient state in the absence of nigrostriatal degeneration. Although l-dopa-induced dyskinesias in tyrosine hydroxylase deficiency are phenomenologically similar to those that occur in Parkinson's disease, they are different in a number of other respects, suggesting intrinsic differences in the pathophysiologic basis of l-dopa-induced dyskinesias in the 2 conditions. © 2013 Movement Disorder Society.

Discovery of compounds that protect tyrosine hydroxylase activity through different mechanisms

“…Most patients are type A and generally respond well to L-Dopa treatment, in fact presenting a Dopa-responsive dystonia phenotype. However, L-Dopa treatment is often associated with low long-term efficiency and secondary effects [7,8]. Furthermore, type B patients are often poor-or non-responders to L-Dopa [7], and new therapeutic alternatives are therefore necessary for these severely affected patients.…”

Dopa-responsive dystonia—clinical and genetic heterogeneity

“…70 Levodopa-induced dyskinesia is more common among patients with tyrosine hydroxylase deficiency than among patients with GTP-CH-I deficiency, and is usually seen within a few months of starting treatment, regardless of the patient's age. 108,115 This dyskinesia is similar to that seen in the treatment of PD, and consists of choreic or stereotypical movements of the limbs, face and trunk. 115,116 The dyskinesia can also manifest as dystonia, such as jawopening dystonia.…”

“…108,115 This dyskinesia is similar to that seen in the treatment of PD, and consists of choreic or stereotypical movements of the limbs, face and trunk. 115,116 The dyskinesia can also manifest as dystonia, such as jawopening dystonia. 115 Measures such as reduction of the levodopa dose can reduce the dyskinesia, and amantadine has also helped in some patients.…”

“…115 Measures such as reduction of the levodopa dose can reduce the dyskinesia, and amantadine has also helped in some patients. 115 Sepiapterin reductase deficiency Most patients with sepiapterin reductase deficiency exhibit a dramatic response to low doses of levodopa, which improves dystonia, spasticity, pyramidal signs, oculogyric crisis, concentration and overall cognitive function. 83,84,87 One study reported a marked improvement in cognitive ability-especially use of language and performance at school-with levodopa treatment in two patients with sepiapterin reductase deficiency, although these children still did not reach normal academic performance for their age.…”

“…115,116 The dyskinesia can also manifest as dystonia, such as jawopening dystonia. 115 Measures such as reduction of the levodopa dose can reduce the dyskinesia, and amantadine has also helped in some patients. 115 Sepiapterin reductase deficiency Most patients with sepiapterin reductase deficiency exhibit a dramatic response to low doses of levodopa, which improves dystonia, spasticity, pyramidal signs, oculogyric crisis, concentration and overall cognitive function.…”