Tyrosine Hydroxylase Deficiency (THD)

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. 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 (HVA) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), with normal 5-hydroxyindoleacetic acid (5-HIAA) cerebrospinal fluid (CSF) concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The HVA concentrations and HVA/ 5-HIAA acid ratio in CSF 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.


Overview of THD:

MA Willemsen, MM Verbeek, RA Wevers, et al: Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain. 2010 Jun;133(Pt 6):1810-22. PUBMED

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