Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Brain. 2010 Jun;133(Pt 6):1810-22. doi: 10.1093/brain/awq087. Epub 2010 Apr 29.

Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis.

Author information

  • 1Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Paediatric Neurology (820 IKNC), PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.willemsen@cukz.umcn.nl

Abstract

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.

PMID:
20430833
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk