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Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis.
- Source :
-
Brain : a journal of neurology [Brain] 2010 Jun; Vol. 133 (Pt 6), pp. 1810-22. Date of Electronic Publication: 2010 Apr 29. - Publication Year :
- 2010
-
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.
- Subjects :
- Age of Onset
Brain Diseases drug therapy
Brain Diseases genetics
Brain Diseases metabolism
Child, Preschool
Disease Progression
Dopamine Agents therapeutic use
Homovanillic Acid cerebrospinal fluid
Humans
Hydroxyindoleacetic Acid cerebrospinal fluid
Hypokinesia drug therapy
Hypokinesia genetics
Hypokinesia metabolism
Infant
Levodopa therapeutic use
Muscle Rigidity drug therapy
Muscle Rigidity genetics
Muscle Rigidity metabolism
Mutation, Missense
Phenotype
Promoter Regions, Genetic
Severity of Illness Index
Tyrosine 3-Monooxygenase genetics
Amino Acid Metabolism, Inborn Errors drug therapy
Amino Acid Metabolism, Inborn Errors genetics
Amino Acid Metabolism, Inborn Errors metabolism
Brain metabolism
Catecholamines biosynthesis
Tyrosine 3-Monooxygenase deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2156
- Volume :
- 133
- Issue :
- Pt 6
- Database :
- MEDLINE
- Journal :
- Brain : a journal of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 20430833
- Full Text :
- https://doi.org/10.1093/brain/awq087