Document Detail

Multiple organ failure due to 5-fluorouracil chemotherapy in a patient with a rare dihydropyrimidine dehydrogenase gene variant.
MedLine Citation:
PMID:  15591715     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the metabolism of the chemotherapeutic drug 5-fluorouracil (5-FU). Application of 5-FU is restricted by a narrow therapeutic index because of severe toxicity of WHO grades III-IV. The exon 14-skipping mutation (c.1905+1G>A) accounts for approximately a quarter of all severely toxic cases. However, numerous other polymorphisms have been identified within the DPYD gene in affected patients, and the pathophysiological significance of most of them is unclear. PATIENT AND METHODS: We report a patient with advanced caecum cancer who twice received 950 mg 5-FU and 45 mg folinic acid as adjuvant by bolus injection. 2 days after onset of chemotherapy, the patient developed a multiple organ dysfunction exhibiting a cardiogenic shock with severe left ventricular insufficiency, marked reduction of renal function, and beginning hepatic encephalopathy with somnolence, myoclonus, and a seizure. In order to investigate a possible defect within the DPYD gene direct sequencing of all 23 exons was carried out. RESULTS: Genotyping revealed a rare c.1601G>A polymorphism which causes a change in the protein sequence (S534N). Data regarding the clinical relevance are ambiguous. The polymorphism has been detected together with an intronic mutation and both polymorphisms have consistently been reported with reduced enzyme activity. CONCLUSION: The present case provides further evidence of an etiologic role of the c.1601G>A mutation for DPD deficiency and the occurrence of severe 5-FU-related toxicity and underlines the value of comprehensive pharmakogenetic diagnostics with respect to the dihydropyrimidine dehydrogenase.
A Lazar; U A Mau-Holzmann; H Kolb; H E Reichenmiller; O Riess; E Schömig
Related Documents :
6340805 - Genetics of glossina morsitans morsitans (diptera: glossinidae). vii. location of g6pd ...
17874335 - Genetic, biochemical, and molecular characterization of nine glyceraldehyde-3-phosphate...
7573035 - An amino acid substitution in the pyruvate dehydrogenase e1 alpha gene, affecting mitoc...
11470705 - Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus alb...
25196645 - Single nucleotide polymorphisms of ataxia telangiectasia mutated and the risk of papill...
19552595 - A genome-wide scan for the sasang constitution in a korean family suggests significant ...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Onkologie     Volume:  27     ISSN:  0378-584X     ISO Abbreviation:  Onkologie     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-13     Completed Date:  2005-02-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7808556     Medline TA:  Onkologie     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  559-62     Citation Subset:  IM    
Institut für Pharmakologie, Klinikum der Universität zu Köln, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adenocarcinoma / drug therapy,  enzymology,  genetics
Antineoplastic Agents / adverse effects,  therapeutic use
Cecal Neoplasms / drug therapy*,  enzymology*,  genetics
Dihydrouracil Dehydrogenase (NADP) / analysis,  deficiency*,  genetics
Fluorouracil / adverse effects*,  therapeutic use*
Genetic Predisposition to Disease / genetics
Metabolic Diseases / complications,  diagnosis*,  enzymology*,  genetics
Multiple Organ Failure / chemically induced*
Rare Diseases / complications,  diagnosis,  enzymology,  genetics
Treatment Outcome
Reg. No./Substance:
0/Antineoplastic Agents; 51-21-8/Fluorouracil; EC Dehydrogenase (NADP)
Comment In:
Onkologie. 2004 Dec;27(6):531-3   [PMID:  15603058 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Response of progressive fibromatosis to therapy with liposomal doxorubicin.
Next Document:  Acute interstitial pneumopathy associated with docetaxel hypersensitivity.