Thus, we hypothesized that in CF patients the intracellular non-methylated folates are accumulated, while the 5-MTHF is not produced, most likely due to alterations of MTHFR activity (Fig. 2C), as also supported by the normality of vitamin B12 cell content, whose deficiency can contribute to folate trapping in cells (Fig. 2B) [59], [60]. The gene discussed is MTHFR; the disease is cystic fibrosis.