Albertine Donker

Chapter 9 306 LOOKING BACKWARDS: STRENGTHS AND LIMITATIONS Strengths of this thesis Extensive laboratory research during the last 20 years has answered many questions regarding both the physiology and pathophysiology of systemic and cellular iron homeostasis. 5,6 Several genes have been discovered that play a pivotal role in microcytic anemias due to genetic disorders of ironmetabolismand heme synthesis. 7-10 However, clinical studies addressing the accurate diagnosis and adequate treatment of these anemias are relatively scarce. The power of the descriptive and diagnostic studies in this thesis lies in our patient-centered point of view, thereby bridging the gap between basis science and clinical practice. The systematic approach of our evidence-based guidelines in combination ( Chapter 3 1 ) with the extensive description of the phenotypes and genotypes in our case series ( Chapter 4 2 and Chapter 6 3 ) will help the clinician in distinguishing these rare disorders from the far more common causes of microcytic anemia due to an acquired iron deficit or due to a thalassemia syndrome. Apart from adults, we paid attention to children in our studies, especially in Chapter 2 and Chapter 7 . 4 This is crucial; the very first lesson we learned as residents in pediatrics was: children are not just small adults. Children have specific anatomical and physiological characteristics that change and mature during the journey from fetal life to adulthood. That is also true for the regulation of systemic and cellular iron handling ( Chapter 2 ); the dynamic process of growth and development provides an extra challenge for clinicians to accurately diagnose and treat iron disorders in childhood. Therefore, the establishment of standardized pediatric serum hepcidin ranges and hepcidin ratios relative to indicators of body iron is an important step in elucidating the physiology of iron metabolism during the successive maturation stages of human life and in facilitating the pediatrician dealing with children with (suspected) genetic and acquired iron disorders. Importantly, for the determination of serum hepcidin levels in our diagnostic studies ( Chapter 7 4 and Chapter 8 ) we used a hepcidin assay that was standardized with our commutable 2 nd reference material (RM), value-assigned by a candidate primary RM. 11 Both clinical care and research in the field of genetic and acquired iron disorders would benefit from comparability of laboratory results independent of time, place,