Biochemical hallmarks of tyrosine hydroxylase deficiency

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 1998-09, Vol.44 (9), p.1897-1904
• Main Authors: Brautigam, Christa, Wevers, Ron A, Jansen, Riet J. T, Smeitink, Jan A. M, Andel, Johanneke F. de Rijk-van, Gabreels, Fons J. M, Hoffmann, Georg F
• Format: Article
• Language: English
• Subjects: Adolescent; Age Factors; Biological and medical sciences; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Biomarkers - urine; Carbidopa - therapeutic use; Cerebrospinal fluid (biochemistry, cytology, circulation, manometry). Intracranial pressure determination; Child; Child, Preschool; Dopamine Agents - therapeutic use; Drug Therapy, Combination; Dystonia - blood; Dystonia - cerebrospinal fluid; Dystonia - drug therapy; Dystonia - urine; Female; Humans; Infant; Investigative techniques, diagnostic techniques (general aspects); Levodopa - therapeutic use; Male; Medical sciences; Nervous system; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reference Values; Specimen Handling; Tyrosine 3-Monooxygenase - deficiency
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/44.9.1897

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 from different parts of the Netherlands were found homozygous for a mutation in exon 6 (G698A) of the TH gene, and one patient was found compound heterozygous for the same mutation and an additional mutation in exon 3. The first clinical symptoms of hypokinesia, rigidity of arms and legs and axial hypotonia, developed between 3 and 7 months of age. Cerebrospinal fluid investigations revealed a characteristic metabolite constellation in every case: low homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethyleneglycol concentrations in the presence of normal reference range 5-hydroxyindolacetic acid concentrations. Strict adherence to a standardized lumbar puncture protocol and adequate age-related reference values are essential for diagnosis of this "new" treatable neurometabolic disorder. Urinary measurements of HVA, vanillylmandelic acid, and catecholamines can lead to false-negative conclusions. All patients showed a remarkable clinical improvement on a low dose of L-dihydroxyphenylalanine/ (S)-2-(3,4-dihydroxybenzyl)-2-hydrazinpropionic acid. During treatment, cerebrospinal fluid HVA, and 3-methoxy-4-hydroxy-phenylethyleneglycol increased substantially.