Albertine Donker

Rare Inherited Iron and Heme-related Anemias 113 3 Table 1. Continued 1B. Ferroportin disease due to defects in SLC40A1 Clinical presentation and diagnostics • Ferroportin disease due to loss-of -function (LOF) mutations should not be considered as a cause of microcytic anemia. • When anemia occurs in a patient with primary iron overload during treatment with repeated phlebotomies the presence of LOF ferroportin disease may be considered. Treatment • Patients with iron overload due to LOF and gain-of-function (GOF) ferroportin disease should be treated with repeated phlebotomies. • For patients that develop anemia during phlebotomies despite elevated ferritin levels extension of the phlebotomy interval is recommended • In patients who develop anemia during phlebotomies additional treatment with EPO may be considered. Family screening* • The proband should be informed about the autosomal dominant inheritance pattern of ferroportin disease. • We recommend screening the first-degree relatives (parents, siblings and children) and additional family members (via cascade screening) for the SLC40A1 mutation identified in the proband. Mutation carriers should be screened for the ferroportin disease phenotype. 1C. Aceruloplasminemia (ACP) due to defects in CP Clinical presentation and diagnostics • In patients with the combination of insulin dependent diabetes, neurodegenerative disease, retinal degeneration and mild anemia with systemic iron loading, CP defects should be considered. • In patient with absent or very low ceruloplasmin in combination with low serum copper and iron, high serum ferritin, and characteristic findings on MRI that are compatible with iron accumulation in liver, pancreas and brain, ACP should be considered. • In case of homozygous or compound heterozygous CP defects, ACP should be diagnosed. Treatment • In patients with ACP anemia is mild and therefore treatment is not recommended. • Iron chelation therapy should be considered for the treatment of ACP. Family screening* • The proband should be informed about the autosomal recessive inheritance pattern of ACP. Siblings of the proband may be also affected. Since CP defects are very rare, the chance that children of the proband are affected is negligible. • We recommend to screen for pathogenic CP mutations: siblings and spouse in case of consanguinity and reproductive age. In case a proband is diagnosed with ACP after the fourth decade, his or her parents are not likely to be of reproductive age, and genotyping is not recommended. • Children of the proband should only be checked for CP mutations in case of consanguinity of the proband and his/her spouse or in case of proven carriership of both proband and his/her spouse. • Indviduals heterozygous or compound heterozygous for CP mutation should be screened for the ACP disease phenotype.