This article includes discussion of tyrosine hydroxylase deficiency and autosomal recessive dopa-responsive dystonia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Tyrosine hydroxylase deficiency is an autosomal recessively inherited inborn error of metabolism that involves the biosynthesis of catecholamines (dopamine, epinephrine, and norepinephrine). The clinical presentation ranges from severe infantile parkinsonism to a phenotype reminiscent of dopa-responsive dystonia. Diagnosis is based on the pattern of monoamine metabolites in CSF.
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• Tyrosine hydroxylase deficiency is an autosomal recessively inherited disorder that leads to a deficient production of catecholamines (dopamine, epinephrine, and norepinephrine).
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• Patients usually exhibit developmental delay, infantile parkinsonism, dystonia, oculogyric crises, and features of autonomic dysfunction. Milder phenotypes may also occur.
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• Tyrosine hydroxylase deficiency is diagnosed by detection of decreased CSF concentrations of the downstream metabolites of catecholamine degradation, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol.
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• The treatment of choice is levodopa; alternatively, patients are treated with other dopaminergic drugs, mainly dopamine agonists and monoamine oxidase inhibitors.
Historical note and terminology
Tyrosine hydroxylase deficiency was first reported in 1971 in 2 brothers with early-onset progressive dopa-responsive dystonia (02). Subsequently, young infants with a more severe phenotype were recognized (12). In 2010, Willemsen and colleagues described the largest series of individuals reported to date (36 patients) and proposed 2 phenotypes: type A, which is less severe, has a better prognosis, and is L-dopa responsive; and type B, which has an early onset, is more severe, and is poorly L-dopa responsive (31). Currently, more than 70 cases have been reported worldwide (31; 06).
In 1996 the first mutations in the tyrosine hydroxylase gene were reported (19). The spectrum of mutations is heterogenous with no hot spots detected (16; 06). Two common mutations due to founder effects have been detected, one in the Greek population (c.707C> T) (23) and another in the Dutch population (c.698G> A) (30).