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A review of biochemical and molecular genetic aspects of tyrosine hydroxylase deficiency including a novel mutation (291delC)
Author(s) -
Wevers R. A.,
Rijkvan Andel J. F.,
Bräutigam C.,
Geurtz B.,
Heuvel L. P. W. J.,
SteenbergenSpanjers G. C. H.,
Smeitink J. A. M.,
Hoffmann G. F.,
Gabreëls F. J. M.
Publication year - 1999
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005539803576
Subject(s) - tyrosine hydroxylase , homovanillic acid , endocrinology , mutation , tyrosine , medicine , exon , vanillylmandelic acid , phenylalanine hydroxylase , tryptophan hydroxylase , biology , genetics , dopamine , gene , biochemistry , serotonin , phenylalanine , serotonergic , receptor , amino acid
An overview is given of the current knowledge on the human tyrosine hydroxylase gene and on the biochemical aspects of diagnosing defects in this gene. Diagnostic biochemical findings are described in four cases of genetically confirmed tyrosine hydroxylase deficiency. Decreased CSF levels of homovanillic acid (HVA) and 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG), together with normal pterin and CSF tyrosine and 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations are the diagnostic hallmarks of tyrosine hydroxylase deficiency. At the metabolite level the diagnosis can only be made reliably in CSF. Strict adherence to a standardized lumbar puncture protocol and adequate reference values are essential for diagnosis of this “new” treatable neurometabolic disorder. Measurements of HVA, vanillylmandelic acid (VMA) or catecholamines in urine are not relevant for diagnosing tyrosine hydroxylase deficiency. The diagnosis should be considered in all children with unexplained hypokinesia and other extrapyramidal symptoms. Three of our patients are homozygous for a mutation in exon 6 (698G>A) of the tyrosine hydroxylase gene and one patient was compound heterozygous for the same mutation and a novel truncating mutation in exon 3 (291delC).