BIOCHEMICAL HALLMARKS OF TYROSINE-HYDROXYLASE DEFICIENCY

We report the biochemical hallmarks of tyrosine hydroxylase deficiency with emphasis on reliable diagnostic strategies of four new cases of an inborn error of tyrosine hydroxylase (TH). Three of our patients fr om different parts of the Netherlands were found homozygous for a muta tion in exon 6 (G698A) of the TH gene, and one patient was found compo und heterozygous for the same mutation and an additional mutation in e xon 3. The first clinical symptoms of hypokinesia, rigidity of arms an d legs and axial hypotonia, developed between 3 and 7 months of age. C erebrospinal fluid investigations revealed a characteristic metabolite constellation in every case: low homovanillic acid (HVA) and 3-methox y-4-hydroxyphenylethyleneglycol concentrations in the presence of norm al reference range 5-hydroxyindolacetic acid concentrations. Strict ad herence to a standardized lumbar puncture protocol and adequate age-re lated reference values are essential for diagnosis of this ''new'' tre atable neurometabolic disorder. Urinary measurements of HVA, vanillylm andelic acid, and catecholamines can lead to false-negative conclusion s. All patients showed a remarkable clinical improvement on a low dose of ne/(S)-2-(3,4-dihydroxybenzyl)-2-hydrazinpropionic acid. During tr eatment, cerebrospinal fluid HVA, and 3-methoxy-4-hydroxy-phenylethyle neglycol increased substantially.