Albertine Donker

Chapter 3 114 Table 1. Continued Part 2: Defects in iron acquisition by the erythroid precursors 2A. Hypotransferrinemia due to defects in TF Clinical presentation and diagnostics • In patients with unexplained hypochromic microcytic anemia, low iron binding capacity/serum transferrin concentrations and increased ferritin concentrations, hypotransferrinemia should be considered. Mutation analysis of the TF gene is recommended. • In case of a homozygous or compound heterozygous TF defect, hypotransferrinemia due to a TF defect should be diagnosed. Treatment • Transferrin supplementation by either plasma transfusion or apo-transferrin infusion is recommended in patients with hypotransferrinemia due to a TF defect. • Iron status should be monitored in patients with hypotransferrinemia due to a TF defect in order to detect toxic iron loading early. • In case of systemic iron loading, phlebotomies are recommended. If phlebotomies are not tolerated due to a decreasing Hb, chelation therapy is recommended. Family screening* • Recommendations are identical to those described in 1C. 2B. Anemia with systemic iron loading due to defects in SLC11A2 (DMT1) Clinical presentation and diagnosis • In patients presenting in childhood with unexplained microcytic anemia with increased TSAT, (among others) SLC11A2 defects should be considered. Genotyping of SLC11A2 is recommended. • In case of a homozygous or compound heterozygous SLC11A2 defect, diagnosis of microcytic anemia due to a SLC11A2 defect is confirmed. Treatment • Patients with microcytic anemia due to pathogenic SLC11A2 defects should be treated with oral iron supplementation and/or EPO and/or erythrocyte transfusions, according to the needs of the individual patient. • In case of treatment with oral iron supplementation and/or erythrocyte transfusions, iron status should be monitored in order to detect toxic iron loading in an early stage. • Since a normal serum ferritin concentration does not exclude liver iron loading in patients with SLC11A2 defects, MRI of the liver should be considered. Family screening* • Recommendations are identical to those described in 1C.