Albertine Donker

Chapter 9 304 STUDIES AT A GLANCE PART I: LITERATURE AND CLINICAL STUDIES We started with a narrative review with the intention to identify the critical roles of iron for the different iron-demanding organ systems during the journey from fetus to adult and to assess the developmental aspects of iron handling, with a focus on the systemic level. We aimed to increase the understanding of iron biology in childhood, therewith enabling a timely and accurate diagnosis of both genetic and acquired iron disorders in children ( Chapter 2 ). After a comprehensive survey of the literature we concluded that iron homeostasis in the growing and developing child is still poorly understood and that appropiate biomarkers for the various iron-consuming organs, especially the central nervous system, are largely absent. This limited comprehension of iron physiology of childhood complicates the diagnosis and management of both acquired iron disorders as iron deficiency (anemia), anemia of inflammation or iron loading due to ineffective erythropoiesis and also of anemias due to genetic disorders of iron metabolism that are addressed in this thesis. For example, lack of pediatric serum hepcidin reference values hamper the diagnosis of TMPRSS6 -related IRIDA. Limited understanding of the optimal iron status for the different iron-consuming tissues in the growing and developing child impede adequate treatment concerning both iron deficiency (ID) and iron overload (IO). Considerations for future research in order to unravel iron handling in childhood are reviewed in the discussion section of Chapter 2 . We continued with a systematic review of the literature on microcytic anemias due to a genetic disorder of iron metabolism or heme synthesis, with the aim of developing evidence-based and multidisciplinary guidelines, aiding the clinician in the diagnosis, treatment and family screening of these rare disorders ( Chapter 3 1 ). We presented such guidelines on 12 disorders of microcytic anemia due to defects in 13 different genes involved in iron metabolism and heme synthesis. We concluded that many aspects of these orphan diseases regarding the pathophysiology, clinical presentation and optimal diagnostic workup and treatment are still unknown, making the level of evidence relatively low. Therefore, we suggested that national and international collaboration between both clinicians and researchers is crucial, in order to improve the clinical care for the involved patients. Suggestions how to shape this cooperation in the field of microcytic anemias due to a genetic disorder of iron metabolism or heme synthesis, are addressed in this chapter. In the next chapters ( Chapter 4 2 and Chapter 6 3 ) we retrospectively described Dutch case series of IRIDA due to TMPRSS6 defects and of