Introduction
Tyrosine hydroxylase deficiency is known as Segawa syndrome, infantile parkinsonism, and L-dopa-responsive dystonia. Tyrosine hydroxylase (TH) deficiency is a rare inherited disorder that affects the nervous system (brain). TH is caused due to genetic disorders, and there are less than 5000 cases in the United States. They are usually seen in newborns or infants, but the definite cause of TH is still unknown. There are two forms of TH deficiency; they are Parkinson’s disease and encephalopathy.
The symptom of triazine hydroxylase deficiency depends from person to person, and clinical features of these conditions overlap with other brain disorders. Some people have more symptoms, and others have mild symptoms. The prognosis of TH deficiency is good, resulting in regaining motor function in children. The motor disorders are prime suspicion of THD, but the proper investigation can rule out potentially treatable disease tyrosine hydroxylase deficiency. Cerebral spinal fluid (CSF) levels and brain imaging confirm THD. THD can best be treated with an initial L-dopa dose in children.
What Is Tyrosine Hydroxylase Deficiency?
Tyrosine hydroxylase (TH) deficiency is a genetic disorder resulting from catecholamine deficiency. The enzyme tyrosine hydroxylase is responsible for catalyzing the hormone named catecholamine, dopamine, epinephrine, and norepinephrine. Dopamine plays an important regulatory role in the nervous system. Dopamine is vital in growth hormone secretion and is responsible for height and pubertal development. In addition, Catecholamine works as a neurotransmitter. A vital function of catecholamine is to transmit information to the brain. Tyrosine hydroxylase plays a crucial role in the biosynthesis of catecholamine. Studies show that complete loss of tyrosine hydroxylase activity is lethal.
What Is the Cause of Tyrosine Hydroxylase Deficiency?
Human tyrosine hydroxylase deficiency is caused due to mutations in the tyrosine hydroxylase (TH) gene on chromosome 11. Tyrosine hydroxylase protein is responsible for catecholamine biosynthesis. Human THD leads to a neurological disorder that affects motor functions such as movement of the limbs. THD does not affect other organs. The brain is affected by minor changes in the TH gene, resulting in brain dysfunction. THD occurs due to mutations (alteration in the gene) in the TH gene. The mutations of the TH gene cause more harmful effects on the protein resulting in the incapability to secrete tyrosine hydroxylase.
What Are the Symptoms of Tyrosine Hydroxylase Deficiency?
Tyrosine hydroxylase deficiency is rare. The symptoms of THD overlap with many neurological disorders. The onset of symptoms was generally seen from the first year of life, within two months to five years. Complex encephalopathy (brain dysfunction) and motor dysfunction are the prime symptoms of THD.
The following are the symptoms of tyrosine hydroxylase deficiency:
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Hypokinesia (a disorder of muscle that results in slow or reduced muscle movement).
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Bradykinesia (impaired or slow movement of the limbs in the body).
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The rigidity of muscles.
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Dystonia (a movement disorder that causes muscle contractions leading to abnormal postures).
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Chorea (abnormal movement disorder that causes involuntary jerk movement).
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Tremor (unintentional shaking movement in the body parts).
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Oculogyric crises (a condition characterized by an involuntary upward deviation of the eyes for a long time).
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Ptosis (a condition characterized by drooping or falling of the upper eyelid).
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Hypersalivation (a condition in which more saliva is produced than usual in the mouth).
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Encephalopathy (brain dysfunction).
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Diurnal fluctuations (altered sleep and wake cycle).
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Weight loss.
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Babinski sign (a sign in which patients move their toe in an upward direction but in the opposite direction of the stimuli like touch).
How Is Tyrosine Hydroxylase Deficiency Diagnosed?
THD is a rare disease and can be treated. Children show unexplained movement disorders, such as tremors or chorea, indicative of neurological disorders.
The following are the ways to diagnose tyrosine hydroxylase deficiency:
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Urine Test - The concentrations of catecholamines in urine help in diagnosing THD.
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Blood Test - Routine blood tests can measure levels of phenylalanine and tyrosine in the body.
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Cerebral Imaging - Patients underwent cerebral MRI studies to observe gross structural abnormalities of the brain and signal changes in the brain.
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Lumbar Puncture - THD can be diagnosed by demonstrating decreased cerebral spinal fluid (CSF) levels. Studies show that THD patients have the lowest concentrations of neurotransmitter metabolites in CSF. Therefore, the performance of a lumbar puncture in children is related to unexplained movement disorders.
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Biochemical Test - THD can be diagnosed by directly measuring enzyme activity in tissue samples and blood cells.
What Is the Treatment of Tyrosine Hydroxylase Deficiency?
The clinical feature is unknown and may overlap with other brain disorders. However, tyrosine hydroxylase deficiency leads to dopamine deficiency in the central nervous system (brain), and treatment with L-dopa is the choice. In addition, the patients who tolerate the dose of L-dopa start gaining motor functions in their limbs.
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Drugs containing L-dopa containing peripheral L-dopa decarboxylase inhibitors (benserazide or carbidopa) are given to the patients to prevent loss of L-dopa in circulation. L-dopa doses range from three to ten mg/kg body weight per day, thrice daily.
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Selegiline can be given for muscle disorders.
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Dopamine-agonists Bromocriptine and Pramipexole can be given to treat motor dysfunction.
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Anticholinergic drugs are prescribed to treat symptoms of THD.
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Benzodiazepines are given to treat dystonia.
Despite long-term treatment during follow-up, it is observed that mild mental retardation occurs in 91 percent of the children. In addition, patients show a decline in social functioning and have decreased school performance.
Conclusion
Tyrosine hydroxylase deficiency is a severe but treatable disease. Lumbar puncture helps to diagnose or rule out potentially treatable disorders such as THD. Most patients with THD can successfully be treated with L-dopa showing the improved quality of life. Patients who tolerated L-dopa showed a good prognosis, and a dramatic improvement in movements due to the disappearance of tremors, rigidity, and dystonia was noted. Patients showed an impressive gain in motor functions and could walk independently during follow-up, and children who had been in a wheelchair for years started to walk again. Proper patient advocacy and support offered by the organizations show an increased recovery rate during treatment.
