tyrosine hydroxylase deficiency

What Is Tyrosine Hydroxylase Deficiency?

Tyrosine hydroxylase deficiency (THD), also called dopa-responsive dystonia, is an inherited movement disorder that causes uncontrollable muscle contractions and developmental delay. Children with THD can have a range of symptoms from mild to very severe. THD is caused by mutations in the TH gene that result in a deficiency in an enzyme called tyrosine hydroxylase. Without it, the amino acid tyrosine cannot properly be converted to dopamine, a key neurotransmitter in the brain. Dopamine is important for many functions, including muscle control and cognition.

In the mild form of THD, symptoms typically begin in childhood, after infancy. Symptoms usually start in the feet or legs. Children develop jerky movements that quickly progress to physical rigidity. Many of the symptoms are described as "parkinsonian" and are similar to those of people who have Parkinson's disease. Children with a mild form of THD generally do not have learning disabilities. If untreated, with time, children with THD may lose the ability to walk and may require a wheelchair. Some children with THD show a diurnal pattern, meaning their symptoms tend to be less severe early in the day and more severe late in the day. With early treatment, children with THD can avoid many or all of the disease's symptoms.

The severe form of the disease will appear in infancy, usually before six months of age. Affected infants have delayed motor skills, weakness in the chest and abdomen, stiffness in the arms and legs, and tremor. Many infants with the disease will have trouble controlling eye movements. These children will eventually have learning disabilities, problems with speech, and behavioral and psychological problems. In addition, some individuals with the disease have problems with their autonomic nervous system, which regulates unconscious functions such as body temperature regulation, digestion, blood-sugar levels, and blood pressure. Treatment of the severe form of the disease may take longer to provide results. The most severe cases of the disease may have little or no success with treatment.

How Common Is Tyrosine Hydroxylase Deficiency?

The prevalence of THD is unknown, and only a small number of cases have been diagnosed globally. Cases have been reported in Japan and in the Netherlands.

How Is Tyrosine Hydroxylase Deficiency Treated?

Individuals with the mild form of THD respond well to treatment with supplements of L-dopa and carbidopa. If these are taken before symptoms appear, the symptoms may be avoided completely. Even if symptoms have already begun, children with the disease often respond extremely well to the medication. If the disease has gone untreated for some time, certain symptoms may remain, including an irregular gait and other mild movement and speech difficulties.

Treatment with L-dopa and carbidopa supplements has been less beneficial for individuals with severe THD, but this treatment may improve motor skills over time.

If symptoms have gone untreated, physical, occupational, and/or speech therapists may prove helpful.

What Is the Prognosis for an Individual with Tyrosine Hydroxylase Deficiency?

With early and consistent treatment, the prognosis for an individual with mild THD is good. Many symptoms can be reversed with treatment. If treatment is not begun early and/or the course of the disease is severe, the individual may be shorter than they would otherwise have been and may have an irregular walk and/or learning disabilities.