Clinical Guidance

Tyrosine hydroxylase (TH) deficiency is associated with a wide phenotypic spectrum. Based on the severity of symptoms and signs as well as responsiveness to levodopa therapy, the three clinical phenotypes from mildest to most severe are: TH-deficient dopa-responsive dystonia (DRD) (DYT5b, DYT-TH); TH-deficient infantile parkinsonism with motor delay; and TH-deficient progressive infantile encephalopathy . In addition, several atypical severe forms have been recognized. None of the symptoms and signs of TH deficiency improve without proper treatment with levodopa .

Diagnostic Criteria

Tyrosine hydroxylase (TH) deficiency is associated with a wide phenotypic spectrum. Based on severity of symptoms and signs as well as responsiveness to levodopa therapy, the three clinical phenotypes attributable to pathogenic variants in TH are: TH-deficient dopa-responsive dystonia (DYT5b, DYT-TH ; the mild form of TH deficiency); TH-deficient infantile parkinsonism with motor delay (the severe form); and TH-deficient progressive infantile encephalopathy (the very severe form). Since clinical suspicion is a key to the diagnosis of TH deficiency, physicians should be aware of this broad phenotypic spectrum.

Suggestive Findings

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with tyrosine hydroxylase (TH) deficiency, the following are recommended if they have not already been completed:

• Clinical examination to assess the severity of motor disturbances

Surveillance Guidelines

Examination by a movement disorder specialist in pediatric or adult neurology at least several times yearly is recommended.

Source: GeneReviews — "Tyrosine Hydroxylase Deficiency"