Albertine Donker

Summary 335 10 SUMMARY Every general practitioner, internist, pediatrician or any other physician will meet patients suffering from anemia during his of her medical career. The worldwide high prevalence of approximately 1.62 billion people, corresponding to 24.8% of the population, makes anemia one of the most common reasons for seeking medical attention in daily clinical practice. Although this condition has numerous causes, diagnostic evaluation is usually straightforward, starting with the determination of the mean corpuscular volume (MCV) of the erytrocytes in order to classify the anemia as microcytic, normocytic of macrocytic. The majority of anemias are microcytic, primarily caused by iron deficiency due to nutritional deficits, gastro-intestinal or gynecological blood loss or iron malabsorption. Furthermore, thalassemia syndromes need to be considered as the cause of microcytic anemias within specific populations. However, in some patients the microcytic anemias cannot be explained by iron deficiency or a hemoglobinopathy. In those cases a genetic disorder of iron metabolism or heme synthesis due to defects in genes involved in systemic and cellular iron metabolism and heme synthesis should be suspected. It is a diagnostic challenge for the clinician to distinguish such rare disorders from the far more common forms of acquired iron deficiency anemia as a result of for example celiac disease or from α- or ß thalassemias. If the treating physician overlooks a microcytic anemia due to a genetic disorder of iron metabolism or heme synthesis, the individual patient may encounter an unnecessarily long diagnostic process and not effective or even harmful treatments. Moreover, in some genetic anemias, such as the sideroblastic anemias, iron overload is of greater clinical consequence than the anemia itself since unrecognized tissue iron loading might lead to severe morbidity and even mortality. The objective of this thesis was to provide the clinician with information on several clinical aspects of microcytic anemias due to a genetic disorder of iron metabolism or heme synthesis with a particular focus on Iron Refractory Iron Deficiency Anemia