Small molecule intervention to dis-inhibit MTHFR, and thereby increase MTHFR activity, could lower the disease burden for severe MTHFR deficiency, a life-threatening metabolic disorder (OMIM #236250; incidence of 1:200,000), characterised by failure to thrive, microcephaly, encephalopathy and seizures [8]. The gene discussed is MTHFR; the disease is hyperinsulinemic hypoglycemia, familial, 4.