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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34595

Willemsen, M A; Verbeek, M M; Kamsteeg, E J; de Rijk-van Andel, J F; Aeby, A; Blau, N; Burlina, A; Donati, M A; Geurtz, B; Grattan-Smith, P J; Haeussler, M; Hoffmann, G F; Jung, H; de Klerk, J B; van der Knaap, M S; Kok, F; Leuzzi, V; de Lonlay, P; Megarbane, A; Monaghan, H; Renier, W O; Rondot, P; Ryan, M M; Seeger, J; Smeitink, J A; Steenbergen-Spanjers, G C; Wassmer, E; Weschke, B; Wijburg, F A; Wilcken, B; Zafeiriou, D I; Wevers, R A (2010). Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain: A Journal of Neurology, 133(6):1810-1822.

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Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:June 2010
Deposited On:05 Jul 2010 12:04
Last Modified:05 Apr 2016 14:10
Publisher:Oxford University Press
Publisher DOI:10.1093/brain/awq087
PubMed ID:20430833

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