Dihydropyrimidine dehydrogenase deficiency

Harris BE, Carpenter JT, Diasio RB. Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common phar-macogenetic syndrome. Cancer 1991 68 499-501. 

Milano G, Etienne MC, Pierrefite V et al. Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br J Cancer 1999 79 627-630. 

Wei X, McLeod HL, McMurrough J et al. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest 1996 98 610-615. 

Johnson MR, Hageboutros A, Wang K et al. life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 1999 5 2006-2011. 

Takimoto, C.H., Lu, Z.H., Zhang, R., et al. (1996) Severe neurotoxicity following 5-fluorour-acil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin. Cancer Res. 2, 477 81. 

Van Kuilenburg AB, VrekenP, Abeling NG et al. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet 1999 104 1-9. 

Boisdron-Celle M, Remaud G, Traore S et al. 5-Fluorouracil-related severe toxicity A comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer Lett 2007 249 271-282. 

Saif MW, Diasio R. Is capecifabine safe in pafienfs wifh gastrointestinal cancer and dihydropyrimidine dehydrogenase deficiency Clin Colorectal Cancer 2006 Jan 5 359-362. 

Al Al-Sanna aNA, Van Kuilenburg AB,Atrak TM et al. Dihydropyrimidine dehydrogenase deficiency presenting at birth. J Inherit Metab Dis 2005 28 793-796. 

A Van Kuilenburg AB, Vreken P, Riva D et al. Clinical and biochemical abnormalities in a patient with dihydropyrimidine dehydrogenase deficiency due to homozygosity for the C29R mutation. JInherited MetabDis 1999 22 91-192. 

Ezzeldin HH, Lee AM, Mattison LK et al. Methylation of the DPYD promoter an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. Clin Cancer Res... 

Ezzeldin H, Okamoto Y, Johnson MR et al. A high-throughput denaturing high-performanee liquid chromatography method for the identification of variant alleles associated with dihydropyrimidine dehydrogenase deficiency. Anal Biochem 2002 306 63-73. 

Saif MW, Mattison L, Carollo T et al. Dihydropyrimidine dehydrogenase deficiency in an Indian population. Cancer Chemother Pharmacol 2006 58 396 01. 

Van Kuilenburg AB, Van Lenthe H, Tromp A et al. Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. Clin Chem 2000 46 9-17. 

Kuhara T, Ohdoi C, Ohse M et al. Rapid gas chromatographic-mass spectrometric diagnosis of dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency. J Chromatogr B Analyt Technol Biomed Life Sci 2003 792 107-115. 

MattisonLK, EzzeldinH, Carpenter Met al. Rapid identification of dihydropyrimidine dehydrogenase deficiency by using a novel 2-13C-uracil breath test. Clin Cancer Pes 2004 10 2652-2658. 

Van Kuilenburg AB, Meinsma R, Zoetekouw L et al. Increased risk of grade IV neutropenia after administration of 5-fiuorouracil due to a dihydropyrimidine dehydrogenase deficiency high prevalence of the 1VS14+1 g>a mutation. Cancer 2002 101 253-258. 

Only a few cases of dihydropyrimidine dehydrogenase deficiency have been identified however, all cases exhibited remarkable toxicity. Enhanced toxicity occurring at normal doses is what usually sets these patients... 

Does dihydropyrimidine dehydrogenase deficiency correlate with the occurrence of severe fluorouracil toxicity ... 

Do individuals with partial dihydropyrimidine dehydrogenase deficiency (that is heterozygotes) have altered metabolism of fluorouracil ... 

Gonzalez, F. J. and Fernandez-Salguero, P. (1995) Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends Pharmacol. Sci. 16, 325-327. 

Dihydropyrimidine dehydrogenase deficiency can cause unexpected toxic effects to 5-fluorouracil administration (see page 641). 

Lee A, Ezzeldin H, Fourie J, et al. Dihydropyrimidine dehydrogenase deficiency impact of pharmacogenetics on 5-fluorouracil therapy. Clin Adv Hematol Oncol 2004 2 527-532. 

Nervous system Fluorouracil can cause acute nervous system toxicity. Acute cerebellar syndrome affects up to 5% of patients and is usually self-limiting after withdrawal. It can occur within weeks to months of starting fluorouracil and presents with ataxia, nystagmus, and dysarthria [77, 78 ]. An encephalopathy can occur rarely and is often associated with markedly raised ammonia concentrations in the absence of underlying liver disease. Ischemic stroke has also been reported and the risk appears to be increased when fluorouracil is combined with cisplatin [60, 79 ]. Other rare adverse reactions include oculomotor disturbances, focal dystonia, parkinsonian syndrome, peripheral neuropathy, and seizures [80 ]. Dihydropyrimidine dehydrogenase deficiency also increases the risk of nervous system toxicity [81" ]. 

Purines and pyrimidines Dihydropyrimidine dehydrogenase deficiency Uracil Tt... 

Table 23.13 Dihydropyrimidine dehydrogenase deficiency [Patients 83 Europe ]...

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