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Hypoxia downregulates protein S expression.

While this manuscript was in preparation, another group of investigators also studied the utility of normalizing plasma hepcidin to the TfSat in patients with IRIDA.6 In particular, they compared the TfSat:hepcidin ratio in TMPRSS6-mutated patients who had 1 or 2 mutated alleles and found that, in general, those individuals with a single detectable allele had a milder biochemical phenotype than those with 2 mutated alleles. We suggest that most patients with a severe clinical phenotype likely have biallelic TMPRSS6 mutations and that, in some cases, the second allele is genetically occult.