Albertine Donker

IRIDA: a Heterogeneous Disease 143 4 METHODS Patients and relatives We included 21 IRIDA patients and their relatives. All IRIDA patients were inhabitants of the Netherlands and consecutively diagnosed between 2010 and 2015. IRIDA probands were defined as patients with both an “IRIDA phenotype” (detected after clinical presentation, microcytic anemia, TSAT < 10%, in the absence of inflammation, Hb and MCV not or partially responsive to oral iron) and an “IRIDA genotype” (a mono- or bi-allelic TMPRSS6 variant that – probably, possibly – affects function, called “defect” hereafter). Iron deficiency anemia in these patients could not be explained (exclusively) by increased physiological needs (growth, menstrual blood loss in premenopausal women), by gastrointestinal disease like Helicobacter Pylori infection, celiac disease of atrophic gastritis 18 or by gynecological problems. Responsiveness to oral iron treatment was defined as a hemoglobin (Hb) increment of 2 g/dL after three weeks of oral iron supplementation. 19 A positive family history for unexplained iron deficiency anemia and anemia presenting in childhood were considered as suspect for IRIDA. Laboratory measurements Hb, red blood cell indices and serum iron parameters were measured in accredited Dutch hospital laboratories. Serum hepcidin measurements were performed by a combination of weak cation exchange and time-of-flight mass spectrometry (WCX-TOF MS). 20,21 The median reference level of serum hepcidin-25 is 4.5 nM for men (p 2.5-p 97.5= < 0.5-14.7 nM), 2.0 nM for premenopausal women (p 2.5-p 97.5=0.1-12.3 nM) and 4.9 nM for postmenopausal women (p 2.5-p 97.5=0.2-15.6 nM). The reference level of serum hepcidin-25 for children aged 0.5 – 3 years is 3.6 nM (p 2.5-p.97.5=0.94-12.2). 22,23 For children > 3 years no reference ranges are available until now, so for this group we recommend using those of premenopausal women. The median reference level of serum TSAT/ hepcidin-25 ratio is 7.3 %/nM for men (p 2.5-p 97.5=1.7-256.3 %/nM), 13.9 %/ nM for premenopausal women (p 2.5-p 97.5=2-330 %/nM) and 5.7 %/nM for postmenopausal women (p 2.5-p97.5=1.5-73.4 %/nM). 23