Tyrosine Hydroxylase Deficiency (Tyrosine hydroxylase deficiency) - Gen TH.
Deficiency tyrosine hydroxylase (TH) is a disorder that primarily affects movement, with symptoms that can range from mild to severe.
The mild form of this disease is called dopa responsive dystonia (DRD) and its symptoms usually appear during childhood. Affected individuals may exhibit an unusual positioning of the limb and a lack of coordination when walking or running. In some cases, people with DRD have additional problems, such as postural tremor or involuntary movements of the eye movement. Movement difficulties can slowly increase with age, but almost always improve with medical treatment.
Meanwhile, severe forms of TH deficiency include child parkinsonism and progressive infantile encephalopathy. These forms of the disease appear shortly after birth and are more difficult to treat effectively. Infants with infantile parkinsonism have delayed development of motor skills, muscle stiffness (especially in the arms and legs), unusual body position, ptosis and involuntary eye movements upwards. In addition, the disease may also affect the autonomic nervous system. Some signs and symptoms may include derivatives constipation, gastroesophageal reflux, and difficulty regulating blood glucose, body temperature and blood pressure. Individuals with parkinsonism child form may have mental retardation, speech problems, attention deficit disorder and psychiatric disorders such as depression, anxiety or obsessive-compulsive behaviors. On the other hand, the progressive infantile encephalopathy is a rare form of severe deficiency of TH. It is characterized by cerebral dysfunction and structural abnormalities that lead to profound mental and physical disabilities.
This process is due to mutations in the TH gene, located on the short arm of chromosome 11 (11p15.5). This gene encodes the enzyme tyrosine hydroxylase, important for the normal functioning of the nervous system. Tyrosine hydroxylase is involved in the pathway that produces catecholamines. Tyrosine hydroxylase helps convert the amino acid tyrosine in a catecholamine called dopamine. Dopamine transmits signals to help the brain control, physical movement and emotional behavior. Other catecholamines, such as norepinephrine and epinephrine, are produced from dopamine. Norepinephrine and epinephrine are involved in the autonomic nervous system.
There are more than 20 mutations in the TH gene deficient individuals tyrosine hydroxylase (TH). These mutations reduced activity of the enzyme tyrosine hydroxylase. As a result, the body produces less dopamine, norepinephrine and epinephrine. These catecholamines are necessary for normal function of the nervous system, and changes in levels contribute to abnormal movements, nervous system dysfunction and other neurological problems seen in people with TH deficiency.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency of tyrosine hydroxylase by the complete PCR amplification of the exons of the TH gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).