In humans, a relationship between HO1 activity and HPX metabolism was first apparent in HO1-deficiency with undetectable HPX levels in a child that succumbed by 6 years (Yachie et al., 1999), as previously reviewed (Smith, 2011b, 2013); and which is recapitulated in part, in HO1−/− mice that also have low HPX (Kovtunovych et al., 2010). Here, HMOX1 is linked to hyperinsulinemic hypoglycemia, familial, 4.