Albertine Donker

Chapter 4 150 All 14 patients diagnosed with a bi-allelic TMPRSS6 defect had been treated with oral iron at referral to our clinic. Of these patients two were responsive to oral iron with a slow, sluggish increase of Hb and MCV (ID 7, ID 11), while patient 13 responded to a combination of oral iron and vitamin C with an increase of Hb, MCV and TSAT. The other 11 bi-allelic patients were unresponsive to oral iron and partially responsive to parenteral iron or blood transfusions in terms of a moderate increase of Hb and MCV, while TSAT remained below 10% in 9 out of 11 patients (ID 8: TSAT 13%, ID 14: TSAT 15% after iron treatment). ( Supplemental Table 1 A and Supplemental Table 3 ). All seven patients diagnosed with a heterozygous TMPRSS6 defect had been treated with oral iron at referral to our clinic, of which two were responsive (ID 19 and 21) with a slow, sluggish increase of Hb, MCV and TSAT. The other 5 patients received intravenous iron supplementation, which resulted in a moderate increase of Hb and MCV. TSAT remained below reference values, except in patient 15. One heterozygous patient (ID 20) received a blood transfusion. Ferritin increased above concentrations of 500 µg/L in three out of 22 patients (patient 8, 14 and 16). Table 1. Continued Patients are ordered according to type of variant. Family studies have confirmed that variants of all compound heterozygous affected patients are located on 2 different alleles. a Hb, MCV, ferritin and TSAT of the proband at time of presentation with anemia; b Hepcidin, TSAT/hepcidin ratio at time of (genotypic) diagnosis of IRIDA, in absence of inflammation except for patient 14 and 20 with CRP levels of 24 and 45 mg/L respectively. 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 yrs is 3.6 nM (p 2.5-p.97.5=0.94-12.2). For children > 3 yrs no reference ranges are available at present, so we recommend for them 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=2.0- 330 %/nM) and 5.7 %/nM for postmenopausal women (p 2.5-p97.5=1.5-73.4 %/nM) (www.hepcidinanalysis. com) 23 c +: has been given, -: has not been given d I, age at presentation with anemia; e II, age at assessing IRIDA and determination of hepcidin and TSAT/hepcidin ratio; f III, age in 2015; g Patient 2 is the daughter of patient 15. However, since both patients presented with anemia at childhood, both were considered as independent probands;