TPMT and hyperinsulinemic hypoglycemia, familial, 4: DPD and TPMT deficiency are the major determinants of severe fluoropyrimidine and thiopurine-associated toxicity, and prospective genotyping followed by genotype-guided prescribing has been shown to reduce adverse events.12,46 Thus, the identification of genetic variations that result in reduced enzyme function is of central importance to improve patient outcomes.