Tyrosine hydroxylase deficiency

Roser Pons MD (Dr. Pons of the University of Athens in Greece has no relevant financial relationships to disclose.)
Barry Wolf MD PhD, editor. (Dr. Wolf of Henry Ford Hospital has no relevant financial relationships to disclose.)
Originally released July 8, 2015; last reviewed March 30, 2016; expires March 30, 2019

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). Patients often exhibit infantile parkinsonism and features of autonomic dysfunction. Diagnosis is based on the pattern of monoamine metabolites in CSF.

Key points


• Tyrosine hydroxylase deficiency is an autosomal recessively inherited disorder that leads to a deficient production of catecholamines (dopamine, epinephrine, and norepinephrine).


• Patients usually exhibit developmental delay, infantile parkinsonism, dystonia, oculogyric crises, and features of autonomic dysfunction. Milder phenotypes may also occur.


• 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.


• 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 (Castaigne et al 1971). Subsequently, young infants with a more severe phenotype were recognized (Hoffmann et al 2003). In 2010, Willemsen and colleagues described the largest series 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 (Willemsen et al 2010). Currently, approximately 70 cases have been reported worldwide (Willemsen et al 2010; Fossbakk et al 2014).

In 1996 the first mutations in the tyrosine hydroxylase gene were reported (Ludecke et al 1996). The spectrum of mutations is heterogenous with no hot spots detected (Kurian et al 2011; Fossbakk et al 2014). Two common mutations due to founder effects have been detected in the Greek population(c.707C>T) and in the Dutch population (c.698G>A) (van den Heuvel et al 1998; Pons 2009).

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