A mild phenotype of dihydropyrimidine dehydrogenase deficiency and developmental retardation associated with a missense mutation affecting cofactor binding

Objectives: Evaluation of a non-synonymous mutation associated with dihydropyrimidine dehydrogenase (DPD) deficiency. Design and methods: DPD enzyme analysis, mutation analysis and molecular dynamics simulations based on the 3D-model of DPD. Results: The substitution Lys63Glu is likely to affect the FAD binding pocket within the DPD protein and contributes to a near-complete DPD deficiency in a patient with developmental retardation. Conclusions: Like other DPD variants attenuating FAD binding, Lys63Glu should be included in screening for DPD deficiency. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.