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Tryptophan 5-monooxygenase deficiency

MedGen UID:
468570
•Concept ID:
CN120491
•
Disease or Syndrome
Synonym: Tryptophan Hydroxylase Deficiency
 
Gene (location): TPH2 (12q21.1)

Professional guidelines

PubMed

HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV).
Pawlowski T, Malyszczak K, Pawlak D, Inglot M, Zalewska M, Grzywacz A, Radkowski M, Laskus T, Janocha-Litwin J, Frydecka D
Cells 2023 Mar 22;12(6) doi: 10.3390/cells12060970. PMID: 36980311Free PMC Article
Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia.
Gallego D, Leal F, Gámez A, Castro M, Navarrete R, Sanchez-Lijarcio O, Vitoria I, Bueno-Delgado M, Belanger-Quintana A, Morais A, Pedrón-Giner C, García I, Campistol J, Artuch R, Alcaide C, Cornejo V, Gil D, Yahyaoui R, Desviat LR, Ugarte M, Martínez A, Pérez B
Hum Mutat 2020 Jul;41(7):1329-1338. Epub 2020 Apr 30 doi: 10.1002/humu.24026. PMID: 32333439
Phenylketonuria: screening, treatment and maternal PKU.
Matalon R, Michals K
Clin Biochem 1991 Aug;24(4):337-42. doi: 10.1016/0009-9120(91)80008-q. PMID: 1959225

Recent clinical studies

Etiology

HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV).
Pawlowski T, Malyszczak K, Pawlak D, Inglot M, Zalewska M, Grzywacz A, Radkowski M, Laskus T, Janocha-Litwin J, Frydecka D
Cells 2023 Mar 22;12(6) doi: 10.3390/cells12060970. PMID: 36980311Free PMC Article
Influence and interaction of resting state functional magnetic resonance and tryptophan hydroxylase-2 methylation on short-term antidepressant drug response.
Tan T, Xu Z, Gao C, Shen T, Li L, Chen Z, Chen L, Xu M, Chen B, Liu J, Zhang Z, Yuan Y
BMC Psychiatry 2022 Mar 25;22(1):218. doi: 10.1186/s12888-022-03860-z. PMID: 35337298Free PMC Article
Tryptophan hydroxylase 2 in seasonal affective disorder: underestimated perspectives?
Kulikov AV, Popova NK
Rev Neurosci 2015;26(6):679-90. doi: 10.1515/revneuro-2015-0013. PMID: 26167977
From genes to aggressive behavior: the role of serotonergic system.
Popova NK
Bioessays 2006 May;28(5):495-503. doi: 10.1002/bies.20412. PMID: 16615082
Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin.
Nagatsu T, Ichinose H
Mol Neurobiol 1999 Feb;19(1):79-96. doi: 10.1007/BF02741379. PMID: 10321973

Diagnosis

Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability.
Anikster Y, Haack TB, Vilboux T, Pode-Shakked B, Thöny B, Shen N, Guarani V, Meissner T, Mayatepek E, Trefz FK, Marek-Yagel D, Martinez A, Huttlin EL, Paulo JA, Berutti R, Benoist JF, Imbard A, Dorboz I, Heimer G, Landau Y, Ziv-Strasser L, Malicdan MCV, Gemperle-Britschgi C, Cremer K, Engels H, Meili D, Keller I, Bruggmann R, Strom TM, Meitinger T, Mullikin JC, Schwartz G, Ben-Zeev B, Gahl WA, Harper JW, Blau N, Hoffmann GF, Prokisch H, Opladen T, Schiff M
Am J Hum Genet 2017 Feb 2;100(2):257-266. Epub 2017 Jan 26 doi: 10.1016/j.ajhg.2017.01.002. PMID: 28132689Free PMC Article
Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease.
Majewski M, Kozlowska A, Thoene M, Lepiarczyk E, Grzegorzewski WJ
J Physiol Pharmacol 2016 Feb;67(1):3-19. PMID: 27010891
The biology of tryptophan depletion and mood disorders.
Toker L, Amar S, Bersudsky Y, Benjamin J, Klein E
Isr J Psychiatry Relat Sci 2010;47(1):46-55. PMID: 20686199
Tryptophan as an evolutionarily conserved signal to brain serotonin: molecular evidence and psychiatric implications.
Russo S, Kema IP, Bosker F, Haavik J, Korf J
World J Biol Psychiatry 2009;10(4):258-68. doi: 10.1080/15622970701513764. PMID: 19921967
Disorders of biopterin metabolism.
Longo N
J Inherit Metab Dis 2009 Jun;32(3):333-42. Epub 2009 Feb 9 doi: 10.1007/s10545-009-1067-2. PMID: 19234759

Therapy

Overproduction of Gastrointestinal 5-HT Promotes Colitis-Associated Colorectal Cancer Progression via Enhancing NLRP3 Inflammasome Activation.
Li T, Fu B, Zhang X, Zhou Y, Yang M, Cao M, Chen Y, Tan Y, Hu R
Cancer Immunol Res 2021 Sep;9(9):1008-1023. Epub 2021 Jul 20 doi: 10.1158/2326-6066.CIR-20-1043. PMID: 34285037
Serotonin, hematopoiesis and stem cells.
Fouquet G, Coman T, Hermine O, Côté F
Pharmacol Res 2019 Feb;140:67-74. Epub 2018 Aug 11 doi: 10.1016/j.phrs.2018.08.005. PMID: 30107202
Peripheral Serotonin Synthesis as a New Drug Target.
Matthes S, Bader M
Trends Pharmacol Sci 2018 Jun;39(6):560-572. Epub 2018 Apr 5 doi: 10.1016/j.tips.2018.03.004. PMID: 29628275
The biology of tryptophan depletion and mood disorders.
Toker L, Amar S, Bersudsky Y, Benjamin J, Klein E
Isr J Psychiatry Relat Sci 2010;47(1):46-55. PMID: 20686199
Tryptophan as a link between psychopathology and somatic states.
Russo S, Kema IP, Fokkema MR, Boon JC, Willemse PH, de Vries EG, den Boer JA, Korf J
Psychosom Med 2003 Jul-Aug;65(4):665-71. doi: 10.1097/01.psy.0000078188.74020.cc. PMID: 12883120

Prognosis

Interplay between the key proteins of serotonin system in SSRI antidepressants efficacy.
Kulikov AV, Gainetdinov RR, Ponimaskin E, Kalueff AV, Naumenko VS, Popova NK
Expert Opin Ther Targets 2018 Apr;22(4):319-330. Epub 2018 Apr 4 doi: 10.1080/14728222.2018.1452912. PMID: 29542343
Peripheral Serotonin 1B Receptor Transcription Predicts the Effect of Acute Tryptophan Depletion on Risky Decision-Making.
Faulkner P, Mancinelli F, Lockwood PL, Matarin M, Dolan RJ, Wood NW, Dayan P, Roiser JP
Int J Neuropsychopharmacol 2017 Jan 1;20(1):58-66. doi: 10.1093/ijnp/pyw075. PMID: 27638901Free PMC Article
Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.
Patrick RP, Ames BN
FASEB J 2014 Jun;28(6):2398-413. Epub 2014 Feb 20 doi: 10.1096/fj.13-246546. PMID: 24558199
The biology of tryptophan depletion and mood disorders.
Toker L, Amar S, Bersudsky Y, Benjamin J, Klein E
Isr J Psychiatry Relat Sci 2010;47(1):46-55. PMID: 20686199
Rapid depletion of plasma tryptophan: a review of studies and experimental methodology.
Reilly JG, McTavish SF, Young AH
J Psychopharmacol 1997;11(4):381-92. doi: 10.1177/026988119701100416. PMID: 9443529

Clinical prediction guides

Developmental delay and non-phenylketonuria (PKU) hyperphenylalaninemia in DNAJC12 deficiency: Case and approach.
Wong RSH, Mohammad S, Parayil Sankaran B, Junek R, Kim WT, Wotton T, Devanapalli B, Bandodkar S, Balasubramaniam S
Brain Dev 2023 Oct;45(9):523-531. Epub 2023 May 6 doi: 10.1016/j.braindev.2023.04.004. PMID: 37156708
Serotonin Deficiency Is Associated With Delayed Gastric Emptying.
Wei L, Singh R, Ha SE, Martin AM, Jones LA, Jin B, Jorgensen BG, Zogg H, Chervo T, Gottfried-Blackmore A, Nguyen L, Habtezion A, Spencer NJ, Keating DJ, Sanders KM, Ro S
Gastroenterology 2021 Jun;160(7):2451-2466.e19. Epub 2021 Mar 2 doi: 10.1053/j.gastro.2021.02.060. PMID: 33662386Free PMC Article
IL-2 regulates tumor-reactive CD8(+) T cell exhaustion by activating the aryl hydrocarbon receptor.
Liu Y, Zhou N, Zhou L, Wang J, Zhou Y, Zhang T, Fang Y, Deng J, Gao Y, Liang X, Lv J, Wang Z, Xie J, Xue Y, Zhang H, Ma J, Tang K, Fang Y, Cheng F, Zhang C, Dong B, Zhao Y, Yuan P, Gao Q, Zhang H, Xiao-Feng Qin F, Huang B
Nat Immunol 2021 Mar;22(3):358-369. Epub 2021 Jan 11 doi: 10.1038/s41590-020-00850-9. PMID: 33432230
Interplay between the key proteins of serotonin system in SSRI antidepressants efficacy.
Kulikov AV, Gainetdinov RR, Ponimaskin E, Kalueff AV, Naumenko VS, Popova NK
Expert Opin Ther Targets 2018 Apr;22(4):319-330. Epub 2018 Apr 4 doi: 10.1080/14728222.2018.1452912. PMID: 29542343
The biology of tryptophan depletion and mood disorders.
Toker L, Amar S, Bersudsky Y, Benjamin J, Klein E
Isr J Psychiatry Relat Sci 2010;47(1):46-55. PMID: 20686199

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