Albertine Donker

Chapter 3 120 Table 2. Overview of characteristics of rare microcytic anemias due to genetic disorders of iron metabolism or heme synthesis Pathophysiology Low iron availability for erythropoiesis Defect in iron acquisition of erythroid progenitor cells Disorder IRIDA Ferroportin disease * Acerulo- plasminemia Hypotrans- ferrinemia Microcytic anemia with iron loading Sideroblastic anemia Gene TMPRSS6 SLC40A1 CP TF DMT1 STEAP3 Protein Matriptase 2 Ferro- portin-1 Cerulo- plasmin Transferrin DMT1 STEAP3 Patients’ desc. 20-100 >200 20-100 5-20 5-20 < 5 (=3) Inheritance AR § AD AR/AD AR AR AR/AD I I Age at present. child adult 40-50 yrs variable child child Symptoms neurological no no yes no no no # skin no no no no no no Anemia variable mild in 10% ++ mild variable variable variable MCV micro normo micro/ normo micro micro micro/ normo b Ring sideroblasts no no no no no yes Iron loading Ferritin no normal-low yes high yes high yes high variable c variable c possible d high d Transferrin saturation <10% normal/ high ++ normal/ low 100% high high Hepcidin high e variable no data low normal /low normal / increased f Treatment oral iron iv iron /EPO g phlebotomy ++ chelation erytx apoTF plasma chelation phlebotomy oral iron erytx EPO chelation erytx EPO chelation * both loss-of function and gain-of function have been described, data in column reflect those of the combined group unless stated otherwise; +, loss-of function; ± , gain-of-function; § ,also autosomal dominant inheritance pattern described; II , heterozygous pathogenic mutation in combination with decreased expression of normal allele; ¶ , in some families only women affected since the defect is lethal in man; # , gonadal dysfunction; ** ,neurologic symptoms manifest in childhood, anemia may develop later in life (young adolescent); ++ , in case of loss-of-function mutations, anemia is more likely to occur and TSAT is lower; a , anemia resolves by pyridoxine treatment in most XLSA patients; b , MCH decreased; c ,