Tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation

Tyrosine hydroxylase (TH) deficiency is generally considered as a cause of the autosomal recessive form of dopa-responsive dystonia, also known as Seg awa disease. Clinical hallmarks comprise parkinsonian and other extrapyrami dal symptoms. Biochemically the defect leads to the defective synthesis of catecholamines, in particular dopamine. The diagnosis relies on a character istic pattern of biogenic amine metabolites exclusively in the CSF and can be confirmed by establishing a mutation in the TH gene. Here we present a p atient meeting all diagnostic criteria, including a new homozygous mutation (926T >C) with confirmed parental heterozygosity, extrapyramidal symptoms, but atypical other symptoms with periodic neurological episodes observed e very 4 days and unresponsive to dopa treatment. The CSF biochemical abnorma lities were severe. Uncharacteristically, a strongly abnormal urinary catec holamine metabolite pattern was also consistently observed. The atypical pr esentation of this patient shows that the clinical and metabolic phenotype of TH deficiency is more variable than formerly thought, and that the condi tion should no longer be considered as a treatable disorder per se.