Albertine Donker

Chapter 3 122 Figure 2. Diagnostic flow chart for microcytic anemias caused by inherited defects in iron metabolism or heme synthesis microcytic anemia additional symptoms yes no neurological dis. photosensitivity isolated ataxia hemolysis yes yes yes no yes no uroporphyrin I and coproporphyrin I accumulation in RBC, plasma urine, faeces FPP accumulation in RBC FPP and ZnPP accumulation in RBC other neur. dis and/or DM serum ceruloplasmin very low / undetectable UROS GATA1 ALAS2* , = FECH CP ABCB7 bone marrow and / or DNA studies Exclude common causes of anemia, like iron deficiency, (severe) anemia of chronic disease, hemoglobinopathies, acquired forms of hemolysis, red cell enzyme deficiencies and membrane defects or bone maroow (failure) disorders ferritin normal / high low-normal / normal TSAT (very) low normal / high severity of anemia severe mild to severe MCV low / normal low SLC25 A38 TMPRSS 6 STEAP3 $ TF SLC40A 1 # ALAS2 DMT1 GLRX5 $ BMRS BMRS BMRS BMRS BMRS BMRS serum transferrin very low / undetectable TSAT severity of anemia high mild to severe MCV low / normal Low TSAT/ hepcidin ratio Genes are given in italics and refer to the disorders of this review (Table 2). After clinical and laboratory assessment, clinicians may proceed to perform a diagnostic workup with either bone marrow smears or gene analysis. Iron parameters should be interpreted in the context of the age of the patient and the given treatment: older patients are more likely to have developed iron overload (increased TSAT and ferritin) due to increased and ineffective erythropoiesis and iron supplementation and transfusions. Note that for some diseases, the decision tree is based on only few patients (Table 2.) *Patients have normocytic anemia and GOF mutation; 1only 1 family described; 6patients have normocytic anemia and the majority have LOF mutations; ^in rare cases, these patients present with elevated ferritin levels Abbreviations: BMRS denotes bone marrow ring sideroblasts; DM, diabetes mellitus; FPP, free protoporphyrin; neur. dis, neurologic disease; ZnPP, zinc protoporphyrin