The first alternative seems unlikely based on the relatively low Km of NADPH for both glutathione reductase (5 to 25 μM [90], [91], [92]) and DHFR (or DHFRL1) (3–4 μM [68]), even with a 30% residual NNT activity such as that observed in the FGD patient reported in this study. This evidence concerns the gene DHFR2 and Aarskog-Scott syndrome, X-linked.