DPYD and hyperinsulinemic hypoglycemia, familial, 4: DPD deficiency leads to increased 5-FU plasma concentration and has been recognized since the 1980s as a main tract of 5-FU-treated subjects undergoing severe adverse events [6,7,8,9], opening the way to the pre-emptive testing of DPD activity level (e.g., phenotypic assessment) to identify patients with high risk for toxicities.