Albertine Donker

General Introduction 27 1 Importantly, hepcidin plays a role as a mediator of antimicrobial activity by causing depletion of extracellular iron, which is thought to be a general defense mechanism against many infections by withholding iron from invading extracellular proliferating pathogens. 87-89 Since (especially young) children are more susceptible to severe life threatening infections, one might argue that relatively high hepcidin levels are favorable in the context of host defense against these extracellular pathogens, 88 outweighing the risk of ID. 14,90 We therefore hypothesize that the set point of systemic iron homeostasis might change during lifetime to adapt to different conditions for which a high amount of iron is relatively favorable or not. Taken together, it is evident that mechanisms for iron absorption, extracellular iron transport and intracellular iron trafficking change during the journey from early life to adulthood, but many questions remain on both the systemic regulation and cellular pathways that are responsible for adjusting iron supply to the needs of the growing and developing child. Addressing these questions in future research will generate insights in physiological changes of systemic and cellular iron homeostasis during human growth and development and will also facilitate the diagnosis, treatment and monitoring of pediatric genetic disorders of iron metabolism or heme synthesis.