TH Gene

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/th

Tyrosine hydroxylase (TH): The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which is important for normal functioning of the nervous system.

genes

1. Normal Function

The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which is important for normal functioning of the nervous system. Tyrosine hydroxylase takes part in the first step of the pathway that produces a group of hormones called catecholamines. This enzyme helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine. Dopamine is also known as a neurotransmitter because it transmits signals between nerve cells in the brain to help control physical movement and emotional behavior. Other catecholamines called norepinephrine and epinephrine are produced from dopamine. Norepinephrine and epinephrine are involved in the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature.

2. Health Conditions Related to Genetic Changes

2.1. Dopa-responsive dystonia

More than two dozen mutations in the TH gene have been found to cause dopa-responsive dystonia. This condition is characterized by a pattern of involuntary muscle contractions (dystonia), tremors, and other uncontrolled movements and usually responds to treatment with a medication called L-Dopa. Most TH gene mutations that cause this condition change single protein building blocks (amino acids) in the tyrosine hydroxylase enzyme, resulting in a decrease in functional enzyme. A reduction in normal tyrosine hydroxylase enzyme leads to a decrease in the production of dopamine, which causes the movement problems characteristic of dopa-responsive dystonia. The amount of functional enzyme that is produced is associated with the severity of the signs and symptoms. Less functional enzyme leads to more severe symptoms.

2.2. Tyrosine hydroxylase deficiency

More than 20 mutations in the TH gene have been identified in people with tyrosine hydroxylase (TH) deficiency. These mutations result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less dopamine, norepinephrine, and epinephrine. These catecholamines are necessary for normal nervous system function, and changes in their levels contribute to the abnormal movements, nervous system dysfunction, and other neurological problems seen in people with TH deficiency.

Dopa-responsive dystonia is sometimes considered a mild form of tyrosine hydroxylase deficiency. It is uncertain whether they are two separate disorders or part of the same disease spectrum.

2.3. Other disorders

Certain common TH variations (polymorphisms) modify catecholamine production, which affects the risk of developing conditions associated with regulation of the autonomic nervous system. These TH gene polymorphisms affect the extent to which blood pressure increases with stress and may increase the risk of high blood pressure (hypertension).

One TH gene polymorphism has been associated with sudden infant death syndrome (SIDS). SIDS is a major cause of death in babies younger than 1 year. It is characterized by sudden and unexplained death, usually during sleep. The polymorphism, called allele *9.3, is the most common TH gene polymorphism among people of European descent and has been identified in a larger percentage of babies who die from SIDS than in other babies. This version of the gene may affect the regulation of breathing or awakening in infants.

3. Other Names for This Gene

DYT5b
TY3H_HUMAN
TYH
tyrosine 3-monooxygenase

References

Furukawa Y, Kish S. Tyrosine Hydroxylase Deficiency. 2008 Feb 8 [updated 2017 May 11]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1437/
Furukawa Y, Kish SJ, Fahn S. Dopa-responsive dystonia due to mild tyrosinehydroxylase deficiency. Ann Neurol. 2004 Jan;55(1):147-8.
Hoffmann GF, Assmann B, Bräutigam C, Dionisi-Vici C, Häussler M, de Klerk JB, Naumann M, Steenbergen-Spanjers GC, Strassburg HM, Wevers RA. Tyrosinehydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsivedystonia. Ann Neurol. 2003;54 Suppl 6:S56-65.
Hunt SC. Tyrosine hydroxylase: another piece of the genetics of hypertensionpuzzle. Circulation. 2007 Aug 28;116(9):970-2.
Klintschar M, Reichenpfader B, Saternus KS. A functional polymorphism in thetyrosine hydroxylase gene indicates a role of noradrenalinergic signaling insudden infant death syndrome. J Pediatr. 2008 Aug;153(2):190-3. doi:10.1016/j.jpeds.2008.02.032.
Pearl PL, Capp PK, Novotny EJ, Gibson KM. Inherited disorders ofneurotransmitters in children and adults. Clin Biochem. 2005 Dec;38(12):1051-8.
Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitterdisorders. J Child Neurol. 2007 May;22(5):606-16. Review.
Rao F, Zhang L, Wessel J, Zhang K, Wen G, Kennedy BP, Rana BK, Das M,Rodriguez-Flores JL, Smith DW, Cadman PE, Salem RM, Mahata SK, Schork NJ,Taupenot L, Ziegler MG, O'Connor DT. Adrenergic polymorphism and the human stressresponse. Ann N Y Acad Sci. 2008 Dec;1148:282-96. doi: 10.1196/annals.1410.085.
Rao F, Zhang L, Wessel J, Zhang K, Wen G, Kennedy BP, Rana BK, Das M,Rodriguez-Flores JL, Smith DW, Cadman PE, Salem RM, Mahata SK, Schork NJ,Taupenot L, Ziegler MG, O'Connor DT. Tyrosine hydroxylase, the rate-limitingenzyme in catecholamine biosynthesis: discovery of common human genetic variants governing transcription, autonomic activity, and blood pressure in vivo.Circulation. 2007 Aug 28;116(9):993-1006.
Schiller A, Wevers RA, Steenbergen GC, Blau N, Jung HH. Long-term course ofL-dopa-responsive dystonia caused by tyrosine hydroxylase deficiency. Neurology. 2004 Oct 26;63(8):1524-6.
Verbeek MM, Steenbergen-Spanjers GC, Willemsen MA, Hol FA, Smeitink J, Seeger J, Grattan-Smith P, Ryan MM, Hoffmann GF, Donati MA, Blau N, Wevers RA. Mutationsin the cyclic adenosine monophosphate response element of the tyrosinehydroxylase gene. Ann Neurol. 2007 Oct;62(4):422-6.
Yeung WL, Wong VC, Chan KY, Hui J, Fung CW, Yau E, Ko CH, Lam CW, Mak CM, Siu S, Low L. Expanding phenotype and clinical analysis of tyrosine hydroxylasedeficiency. J Child Neurol. 2011 Feb;26(2):179-87. doi: 10.1177/0883073810377014.
Zhang L, Rao F, Wessel J, Kennedy BP, Rana BK, Taupenot L, Lillie EO, CockburnM, Schork NJ, Ziegler MG, O'Connor DT. Functional allelic heterogeneity andpleiotropy of a repeat polymorphism in tyrosine hydroxylase: prediction ofcatecholamines and response to stress in twins. Physiol Genomics. 2004 Nov17;19(3):277-91.

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Rui Liu

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