Moreover, the mutual NTD-exacerbating pairwise interactions of folate deficiency, Shmt1 loss of function and Pax3 mutation further implicate thymidylate synthase as an FA-sensitive process for neural tube closure (Beaudin et al., 2011; Burren et al., 2008; Martiniova et al., 2015). Here, SHMT1 is linked to hyperinsulinemic hypoglycemia, familial, 4.