Albertine Donker

Chapter 3 104 Treatment Treatment consists of infusions of apo-transferrin either directly or as plasma. Data on the dosage and frequency of these infusions are limited. Monthly infusions of plasma have been reported to be sufficient to normalize Hb and serum ferritin levels. To date, only three patients have been treated with apo-transferrin on a compassionate use-basis. 50,55 The calculated elimination half-life reported varied between 4.8 and 10 days. Apo-transferrin is not on the market for clinical purposes but has an orphan drug status (EU/3/12/1027; 2012). A clinical trial in patients with hypotransferrinemia is ongoing (ClinicalTrials.gov Identifier: NCT01797055). Reluctance with repeated erythrocyte transfusion or iron substitution is advocated to avoid further iron overload. 2B. Anemia with systemic iron loading due to defects in SLC11A2 (DMT1) Pathogenesis and epidemiology SLC11A2 (OMIM 600523) encodes Divalent Metal Transporter-1 (DMT1), a cellular membrane bound iron transporter ( Figure 1 ). 1 , 57,58 Molecular studies indicate that SLC11A2 defects cause defective enterocyte and erythroid iron uptake. 59 Systemic iron loading suggests the presence of an additional pathway for intestinal iron absorption, e.g. as heme. 60 Another explanation might be the low hepcidin levels, resulting in increased dietary iron absorption in case SLC11A2 is not completely eliminated. 61 Anemia with systemic iron loading due to defects in SLC11A2 is a rare autosomal recessive disorder: Seven patients from six families have been described due to homozygous (n=2) or compound heterozygous defects (n=5). Clinical presentation, diagnosis Four out of seven described patients presented at birth with microcytic anemia and increased TSAT. Serum ferritin levels varied from low to moderately increased, with some association with erythrocyte transfusions or intravenous iron supplementation. Liver iron loading was demonstrated by MRI or biopsy in five out of seven patients at ages varying between 5-27 years despite normal or only mildly increased ferritin concentrations in three of them.