Albertine Donker

IRIDA: a Heterogeneous Disease 157 4 TSAT/hepcidin was significantly lower for bi-allelic IRIDA patients (median: 0.51 %/nM, range 0.13-1.0 %/nM, n=11) than for mono-allelic IRIDA patients (1.0 %/nM, 0.3-2.7 %/ nM, n=7, unpaired t-test p < 0.05). Interestingly, mono-allelic IRIDA patients had lower ratios than their relatives with the same genotype but without an IRIDA phenotype (11 %/nM, 3.1-29 %/nM, n=14, p < 0.001). Among relatives without a phenotype, the ratios were similar for mono-allelic (11 %/nM, 3.1-29 %/nM, n=14) and wild –type subjects (16%/nM, 4.6-38 %/nM, n=4)( Figure 1 ). Figure 1. TSAT/hepcidin ratio in bi-allelic (1a) and mono-allelic (1b) affected IRIDA patients and their clinically not affected relatives (2a, 3a, 3b) 1a 1b 2a 3a 3b 0.1 1 10 100 TSAT/hepcidin ratio (%/nM) * ** TSAT/hepcidin ratio in bi-allelic (1a) and mono-allelic (1b) affected IRIDA patients and their clinically not affected relatives (2a, 3a, 3b, n=38). Patients are defined as having both an IRIDA phenotype (detected after clinical presentation, microcytic anemia, TSAT below the reference range, in the absence of inflammation, not or partially responsive to oral iron) and an IRIDA genotype (a mono- or bi-allelic pathogenic defect in the TMPRSS6 gene). 1. Patients with an IRIDA phenotype; 1a. Probands with bi-allelic TMPRSS6 defect, n=11; 1b. Probands with mono-allelic TMPRSS6 defect, n=6, and affected relative (mother of patient 17) with mono-allelic TMPRSS6 defect, n=1; 2. Relatives without an IRIDA phenotype. 2a. Relatives with bi-allelic TMPRSS6 defect, n=2; 3. Relatives without an IRIDA phenotype; 3a. Relatives with mono-allelic TMPRSS6 defect, n=14; 3b. Wild-type TMPRSS6 relatives, n=4. Patients and relatives with signs of inflammation were excluded from the analysis. Boxes indicate median and interquartile ranges; whiskers describe the range of the data (min–max). *P < 0.05; **P < 0.001 as tested by unpaired t test. Iron oral absorption test in the diagnosis of IRIDA patients To evaluate intestinal iron absorption, an iron oral absorption test (IOAT) was performed in two bi-allelic and three mono-allelic IRIDA patients. 30,,31 In the bi-allelic