Albertine Donker

Rare Inherited Iron and Heme-related Anemias 101 3 We conclude that of the total of 76 patients diagnosed with iron overload due to both LOF and GOF mutations in SLC40A1 and documented Hb levels only ≈ 10% was anemic. This anemia is described as mild and normocytic. Treatment Iron overload in patients with both LOF and GOF ferroportin disease is treated with phlebotomy. Both the application of phlebotomy and its effects were described for 94 patients. In 14 of the 94 patients (14.8%) a transient mild or profound anemia during phlebotomy treatment was reported.Our literature evaluation showed that the risk for the development of anemia during phlebotomy was associated with older age and a LOF mutation phenotype, e.g. a relatively low TSAT ( Table 2 in Supplement 3 ). Data from case reports suggest that patients who develop anemia upon phlebotomies benefit from extension of the phlebotomy interval. 1C. Aceruloplasminemia (ACP) due to defects in CP Pathogenesis and epidemiology CP (OMIM 604290) encodes ceruloplasmin (CP), which is secreted into plasma and carries 95 % of circulating plasma copper. CP catalyzes cellular efflux of iron by oxidation of Fe 2+ to Fe 3+ for binding to circulating transferrin ( Figure 1 ). 36 In vitro studies and mice studies show that CP is also required for the stability of the iron exporter ferroportin, especially in glial cells. 37 Mice studies demonstrate that the absence of CP leads to wide spread iron overload in parenchymal and reticuloendothelial organs, including the nervous system. 36 The incidence of ACP in Japan is estimated to be approximately 1 per 2,000,000 in non-consanguineous marriages. There are no reliable data on the incidence and prevalence in Western European countries. 38 In total 35 pathogenic CP mutations have been described in 50 families. ACP is a rare autosomal recessive disease. However, seven patients with a clinical phenotype of ACP were heterozygous for a CP defect ( Supplement 1, online ). Clinical presentation and diagnosis Iron accumulation in ACP affects the liver, pancreas and central nervous system. 39 ACP patients develop the classical triad of i) diabetes mellitus, ii) retinal degeneration and iii) neurodegenerative disease with extrapyramidal and cerebellar symptoms in