HMOX1 and hyperinsulinemic hypoglycemia, familial, 4: In the clinic, hypoferremia (iron-deficiency) and heme-catabolizing enzyme deficiencies (e.g., HO-1 deficiency) can cause progressive depletion of erythrophagocytic macrophage populations, profoundly deregulating heme-iron metabolism and homeostasis (Guida et al., 2015; Soares and Hamza, 2016).