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DOI: 10.1055/s-2005-916301
TH mutations in dopa-responsiv dystonia
Tyrosine hydroxylase (TH) catalyze the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-dopa), the rate-limiting step in the biosynthesis of the catecholamines dopamine, norepinephrine and epinephrine. We have developed a mutation screening method using denaturing gradient gel electrophoresis (DGGE) for rapid analysis for mutations in the coding sequence of the TH gene. We have identified the mutations in 9 patients suffering from TH deficiency due to TH mutations. The major part of the mutations affect conserved residues located in the catalytic domain of the Tyrosine hydroxylase, but also residues located in the regulatory domain or the tetramerization domain was affected. The patients represent a wide range of phenotypes, from an unremarkable mild form of TH deficiency with onset from 10–16 years old and a complete or almost complete resolutions of symptoms by L-dopa treatment to a very early onset at about 3 month, presenting with dyskinesia, hypotonia and hyperreflexia in spite of L-dopa treatment. We conclude that TH mutations leads to a wide range of phenotypes from late onset and a complete resolution to L-dopa therapy to a lethal metabolic disorder with a very early, even prenatal, onset.