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Dihydropyrimidinurias

MedGen UID:
501200
Concept ID:
C3495551
Disease or Syndrome
Synonym: Dihydropyrimidinuria
 
OMIM®: 222748

Definition

Dihydropyrimidinase (DPD) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. Asymptomatic cases are also reported. DPD deficiency increases the risk of 5-FU toxicity. [from ORPHANET]

Professional guidelines

PubMed

Etienne-Grimaldi MC, Pallet N, Boige V, Ciccolini J, Chouchana L, Barin-Le Guellec C, Zaanan A, Narjoz C, Taieb J, Thomas F, Loriot MA; Francophone Network of Pharmacogenetics (RNPGx) and the French Clinical Oncopharmacology Group (GPCO)-UNICANCER
Eur J Cancer 2023 Mar;181:3-17. Epub 2022 Dec 9 doi: 10.1016/j.ejca.2022.11.028. PMID: 36621118
García-Alfonso P, Saiz-Rodríguez M, Mondéjar R, Salazar J, Páez D, Borobia AM, Safont MJ, García-García I, Colomer R, García-González X, Herrero MJ, López-Fernández LA, Abad-Santos F
Clin Transl Oncol 2022 Mar;24(3):483-494. Epub 2021 Nov 13 doi: 10.1007/s12094-021-02708-4. PMID: 34773566Free PMC Article
Wörmann B, Bokemeyer C, Burmeister T, Köhne CH, Schwab M, Arnold D, Blohmer JU, Borner M, Brucker S, Cascorbi I, Decker T, de Wit M, Dietz A, Einsele H, Eisterer W, Folprecht G, Hilbe W, Hoffmann J, Knauf W, Kunzmann V, Largiadèr CR, Lorenzen S, Lüftner D, Moehler M, Nöthen MM, Pox C, Reinacher-Schick A, Scharl A, Schlegelberger B, Seufferlein T, Sinn M, Stroth M, Tamm I, Trümper L, Wilhelm M, Wöll E, Hofheinz RD
Oncol Res Treat 2020;43(11):628-636. Epub 2020 Oct 23 doi: 10.1159/000510258. PMID: 33099551

Recent clinical studies

Etiology

de With M, Sadlon A, Cecchin E, Haufroid V, Thomas F, Joerger M, van Schaik RHN, Mathijssen RHJ, Largiadèr CR; ‘The Working Group on the Implementation of DPD-deficiency Testing in Europe’
ESMO Open 2023 Apr;8(2):101197. Epub 2023 Mar 28 doi: 10.1016/j.esmoop.2023.101197. PMID: 36989883Free PMC Article
Etienne-Grimaldi MC, Pallet N, Boige V, Ciccolini J, Chouchana L, Barin-Le Guellec C, Zaanan A, Narjoz C, Taieb J, Thomas F, Loriot MA; Francophone Network of Pharmacogenetics (RNPGx) and the French Clinical Oncopharmacology Group (GPCO)-UNICANCER
Eur J Cancer 2023 Mar;181:3-17. Epub 2022 Dec 9 doi: 10.1016/j.ejca.2022.11.028. PMID: 36621118
White C, Scott RJ, Paul C, Ziolkowski A, Mossman D, Fox SB, Michael M, Ackland S
Clin Pharmacol Ther 2022 Oct;112(4):791-802. Epub 2022 Jun 12 doi: 10.1002/cpt.2667. PMID: 35607723
Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, Leone F
Crit Rev Oncol Hematol 2018 Apr;124:1-10. Epub 2018 Feb 7 doi: 10.1016/j.critrevonc.2018.02.002. PMID: 29548480
Patel JN, Papachristos A
Cancer Chemother Pharmacol 2015 Nov;76(5):879-96. Epub 2015 Aug 23 doi: 10.1007/s00280-015-2849-x. PMID: 26298089

Diagnosis

de With M, Sadlon A, Cecchin E, Haufroid V, Thomas F, Joerger M, van Schaik RHN, Mathijssen RHJ, Largiadèr CR; ‘The Working Group on the Implementation of DPD-deficiency Testing in Europe’
ESMO Open 2023 Apr;8(2):101197. Epub 2023 Mar 28 doi: 10.1016/j.esmoop.2023.101197. PMID: 36989883Free PMC Article
Etienne-Grimaldi MC, Pallet N, Boige V, Ciccolini J, Chouchana L, Barin-Le Guellec C, Zaanan A, Narjoz C, Taieb J, Thomas F, Loriot MA; Francophone Network of Pharmacogenetics (RNPGx) and the French Clinical Oncopharmacology Group (GPCO)-UNICANCER
Eur J Cancer 2023 Mar;181:3-17. Epub 2022 Dec 9 doi: 10.1016/j.ejca.2022.11.028. PMID: 36621118
Taieb J, Karoui M, Basile D
ESMO Open 2021 Aug;6(4):100184. Epub 2021 Jul 5 doi: 10.1016/j.esmoop.2021.100184. PMID: 34237612Free PMC Article
Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, Leone F
Crit Rev Oncol Hematol 2018 Apr;124:1-10. Epub 2018 Feb 7 doi: 10.1016/j.critrevonc.2018.02.002. PMID: 29548480
Lunenburg CATC, Henricks LM, Guchelaar HJ, Swen JJ, Deenen MJ, Schellens JHM, Gelderblom H
Eur J Cancer 2016 Feb;54:40-48. Epub 2015 Dec 21 doi: 10.1016/j.ejca.2015.11.008. PMID: 26716401

Therapy

de With M, Sadlon A, Cecchin E, Haufroid V, Thomas F, Joerger M, van Schaik RHN, Mathijssen RHJ, Largiadèr CR; ‘The Working Group on the Implementation of DPD-deficiency Testing in Europe’
ESMO Open 2023 Apr;8(2):101197. Epub 2023 Mar 28 doi: 10.1016/j.esmoop.2023.101197. PMID: 36989883Free PMC Article
Etienne-Grimaldi MC, Pallet N, Boige V, Ciccolini J, Chouchana L, Barin-Le Guellec C, Zaanan A, Narjoz C, Taieb J, Thomas F, Loriot MA; Francophone Network of Pharmacogenetics (RNPGx) and the French Clinical Oncopharmacology Group (GPCO)-UNICANCER
Eur J Cancer 2023 Mar;181:3-17. Epub 2022 Dec 9 doi: 10.1016/j.ejca.2022.11.028. PMID: 36621118
White C, Scott RJ, Paul C, Ziolkowski A, Mossman D, Fox SB, Michael M, Ackland S
Clin Pharmacol Ther 2022 Oct;112(4):791-802. Epub 2022 Jun 12 doi: 10.1002/cpt.2667. PMID: 35607723
Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, Leone F
Crit Rev Oncol Hematol 2018 Apr;124:1-10. Epub 2018 Feb 7 doi: 10.1016/j.critrevonc.2018.02.002. PMID: 29548480
Patel JN, Papachristos A
Cancer Chemother Pharmacol 2015 Nov;76(5):879-96. Epub 2015 Aug 23 doi: 10.1007/s00280-015-2849-x. PMID: 26298089

Prognosis

Le Teuff G, Cozic N, Boyer JC, Boige V, Diasio RB, Taieb J, Meulendijks D, Palles C, Schwab M, Deenen M, Largiadèr CR, Marinaki A, Jennings BA, Wettergren Y, Di Paolo A, Gross E, Budai B, Ackland SP, van Kuilenburg ABP, McLeod HL, Milano G, Thomas F, Loriot MA, Kerr D, Schellens JHM, Laurent-Puig P, Shi Q, Pignon JP, Etienne-Grimaldi MC; FUSAFE collaborative group
Br J Cancer 2024 Mar;130(5):808-818. Epub 2024 Jan 15 doi: 10.1038/s41416-023-02517-2. PMID: 38225422Free PMC Article
Lešnjaković L, Ganoci L, Bilić I, Šimičević L, Mucalo I, Pleština S, Božina N
Pharmacogenomics 2023 Jan;24(2):93-106. Epub 2023 Jan 13 doi: 10.2217/pgs-2022-0135. PMID: 36636997
Taieb J, Karoui M, Basile D
ESMO Open 2021 Aug;6(4):100184. Epub 2021 Jul 5 doi: 10.1016/j.esmoop.2021.100184. PMID: 34237612Free PMC Article
Royer B, Schmitt A, Nguyen T, Paillard MJ, Jary M, Demarchi M, Vernerey D, Henriques J, Jacquin M, Borg C, Kim S
Br J Clin Pharmacol 2021 Mar;87(3):1327-1337. Epub 2020 Sep 4 doi: 10.1111/bcp.14519. PMID: 32789966
Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, Leone F
Crit Rev Oncol Hematol 2018 Apr;124:1-10. Epub 2018 Feb 7 doi: 10.1016/j.critrevonc.2018.02.002. PMID: 29548480

Clinical prediction guides

van Karnebeek CDM, Tarailo-Graovac M, Leen R, Meinsma R, Correard S, Jansen-Meijer J, Prykhozhij SV, Pena IA, Ban K, Schock S, Saxena V, Pras-Raves ML, Drögemöller BI, Grootemaat AE, van der Wel NN, Dobritzsch D, Roseboom W, Schomakers BV, Jaspers YRJ, Zoetekouw L, Roelofsen J, Ferreira CR, van der Lee R, Ross CJ, Kochan J, McIntyre RL, van Klinken JB, van Weeghel M, Kramer G, Weschke B, Labrune P, Willemsen MA, Riva D, Garavaglia B, Moeschler JB, Filiano JJ, Ekker M, Berman JN, Dyment D, Vaz FM, Wasserman WW, Houtkooper RH, van Kuilenburg ABP
Genet Med 2024 Jun;26(6):101104. Epub 2024 Feb 24 doi: 10.1016/j.gim.2024.101104. PMID: 38411040
Le Teuff G, Cozic N, Boyer JC, Boige V, Diasio RB, Taieb J, Meulendijks D, Palles C, Schwab M, Deenen M, Largiadèr CR, Marinaki A, Jennings BA, Wettergren Y, Di Paolo A, Gross E, Budai B, Ackland SP, van Kuilenburg ABP, McLeod HL, Milano G, Thomas F, Loriot MA, Kerr D, Schellens JHM, Laurent-Puig P, Shi Q, Pignon JP, Etienne-Grimaldi MC; FUSAFE collaborative group
Br J Cancer 2024 Mar;130(5):808-818. Epub 2024 Jan 15 doi: 10.1038/s41416-023-02517-2. PMID: 38225422Free PMC Article
Lešnjaković L, Ganoci L, Bilić I, Šimičević L, Mucalo I, Pleština S, Božina N
Pharmacogenomics 2023 Jan;24(2):93-106. Epub 2023 Jan 13 doi: 10.2217/pgs-2022-0135. PMID: 36636997
Chavani O
Ther Drug Monit 2020 Oct;42(5):660-664. doi: 10.1097/FTD.0000000000000788. PMID: 32649488
Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, Leone F
Crit Rev Oncol Hematol 2018 Apr;124:1-10. Epub 2018 Feb 7 doi: 10.1016/j.critrevonc.2018.02.002. PMID: 29548480

Recent systematic reviews

Meulendijks D, Henricks LM, Sonke GS, Deenen MJ, Froehlich TK, Amstutz U, Largiadèr CR, Jennings BA, Marinaki AM, Sanderson JD, Kleibl Z, Kleiblova P, Schwab M, Zanger UM, Palles C, Tomlinson I, Gross E, van Kuilenburg AB, Punt CJ, Koopman M, Beijnen JH, Cats A, Schellens JH
Lancet Oncol 2015 Dec;16(16):1639-50. Epub 2015 Oct 23 doi: 10.1016/S1470-2045(15)00286-7. PMID: 26603945
Chung C, Christianson M
J Oncol Pharm Pract 2014 Feb;20(1):11-28. Epub 2013 Mar 14 doi: 10.1177/1078155212474047. PMID: 23493335

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