Tyrosine hydroxylase deficiency

Tyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement. There are three forms of tyrosine hydroxylase deficiency, and they are categorized based on the severity of their symptoms and their response to treatment. The three forms range in severity from mild to severe.

For those with the mild form of tyrosine hydroxylase deficiency (also called TH-deficient dopa-responsive dystonia), symptoms usually appear during childhood. Affected individuals may have difficulties walking and running, which can sometimes lead to falls. Some people with the disorder may walk on their toes because of stiffness in the leg muscles. Additional signs and symptoms may include involuntary muscle contractions (dystonia) that lead to abnormal repetitive movements in the legs, tremor when holding a position (postural tremor), or involuntary upward-rolling movements of the eyes. Symptoms tend to worsen later in the day for some people with TH-deficient dopa-responsive dystonia. Affected individuals may experience more pronounced movement difficulties as they age, but these symptoms almost always get better with medical treatment.

The more severe forms of tyrosine hydroxylase deficiency are often called TH-deficient infantile parkinsonism or TH-deficient progressive infantile encephalopathy. These forms of the disorder appear soon after birth and are more difficult to treat.

Signs and symptoms of TH-deficient infantile parkinsonism typically begin in the first year of life. Affected infants often have delayed development of motor skills such as sitting unsupported or reaching for a toy. Some signs and symptoms may resemble those seen in people with Parkinson disease: stiffness of the muscles in the arms and legs, slow or diminished movements (hypokinesia), and tremors. Additional signs and symptoms may include droopy eyelids (ptosis), involuntary upward-rolling eye movements, and intellectual disabilities. People with TH-deficient infantile parkinsonism may respond to treatment, though treatment may not work right away and may not resolve all of the symptoms of the condition.

The most severe form of tyrosine hydroxylase deficiency (also called TH-deficient progressive infantile encephalopathy) is characterized by brain dysfunction that leads to profound physical and intellectual disabilities. Signs and symptoms typically begin in the first six months of life. Babies with this form of tyrosine hydroxylase deficiency often have feeding difficulties and delayed growth. Additional features include hypokinesia and abnormal eye movements. This form of tyrosine hydroxylase deficiency is difficult to treat, as affected infants tend to be more likely to experience harmful side effects from the medicine.