Tyrosine Hydroxylase Deficiency (THD)

Tyrosine Hydroxylase (TH) deficiency is a rare metabolic disorder characterized by the lack of the enzyme involved in converting the amino acid tyrosine to Ldopa. Tyrosine hydroxylase is a critical enzyme in normal dopamine production. Lack of this enzyme means neurotransmitters are blocked from signaling one another appropriately. The neurotransmitters dopamine, norepinepherine, epinepherine (collectively known as catecholamines) and serotonin are deficient in the central nervous system and periphery.

Patients with TH Deficiency can develop movement disorders, autonomic symptoms (blood pressure instability, temperature irregularities), abnormal eye movements and neurological impairment.

A wide range of symptoms can be associated with TH Deficiency, and involvement can vary from mild, moderate to severe.

Patients may demonstrate all or some of the following symptoms:

• Muscle tightness (rigidity, spasticity)
• Tremor
• Dystonia
• Abnormal posturing (arching of the back)
• Poor muscle control
• Abnormal eye movements (eye deviation upward, downward or towards the nose)
• Strabismus (cross-eyed)
• Ptosis (droopiness of the eyelids)
• Speech delay
• Difficulties feeding or swallowing
• Constipation
• Torticollis (involuntary deviation of the head and neck)
• Intermittent color changes
• Unexplained low body temperatures or fevers
• Low blood sugar
• Difficulty regulating blood pressure

Children who are severely affected are more difficult to treat, and several medications may be needed. They are unusually vulnerable to side effects of the medications, which can result in excessive movement and irritability. Response may be slow, with some continued benefit over months to years, but may not result in the complete resolution of all symptoms. Symptoms may present or worsen during other illnesses the child might experience. Children with TH Deficiency are often considered clumsy or uncoordinated and are often initially diagnosed with cerebral palsy.

TH Deficiency is inherited as an autosomal recessive trait. In recessive disorders, the condition does not occur unless an individual inherits the same defective gene for the same trait from each parent. A child who receives one normal gene and one gene for the disease will be a carrier but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder is 25%. The risk is the same for each pregnancy.

Presently, the most well established treatment of TH Deficiency is medication to help restore normal dopamine levels. Dopamine itself cannot cross the blood-brain barrier directly and so it is necessary to treat with a compound called L-Dopa in combination with another medication called carbidopa. Sinemet is a commercially available medication which contains both carbidopa and L-dopa together in a single tablet. It is important to work closely with the physician to maximize the results of medications and reduce side effects.

Source: http://pndassoc.org/diseases/th.html