| Autor: |
Hoving V; Department of Hematology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GE Nijmegen, The Netherlands., Korman SE; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GE Nijmegen, The Netherlands., Antonopoulos P; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GE Nijmegen, The Netherlands., Donker AE; Department of Pediatrics, Máxima Medical Center, De Run 4600, 5504 NB Veldhoven, The Netherlands., Schols SEM; Department of Hematology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GE Nijmegen, The Netherlands., Swinkels DW; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GE Nijmegen, The Netherlands.; Sanquin Blood Bank, Sanquin Diagnostics BV, Plesmanlaan 125, 1066 NH Amsterdam, The Netherlands. |
| Abstrakt: |
Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive inherited form of iron deficiency anemia characterized by discrepantly high hepcidin levels relative to body iron status. However, patients with monoallelic exonic TMPRSS6 variants have also been reported to express the IRIDA phenotype. The pathogenesis of an IRIDA phenotype in these patients is unknown and causes diagnostic uncertainty. Therefore, we retrospectively summarized the data of 16 patients (4 men, 12 women) who expressed the IRIDA phenotype in the presence of only a monoallelic TMPRSS6 variant. Eight unaffected relatives with identical exonic TMPRSS6 variants were used as controls. Haplotype analysis was performed to assess the (intra)genetic differences between patients and relatives. The expression and severity of the IRIDA phenotype were highly variable. Compared with their relatives, patients showed lower Hb, MCV, and TSAT/hepcidin ratios and inherited a different wild-type allele. We conclude that IRIDA in monoallelic TMPRSS6 -affected patients is a phenotypically and genotypically heterogeneous disease that is more common in female patients. We hypothesize that allelic imbalance, polygenetic inheritance, or modulating environmental factors and their complex interplay are possible causes. This explorative study is the first step toward improved insights into the pathophysiology and improved diagnostic accuracy for patients presenting with IRIDA and a monoallelic exonic TMPRSS6 variant. |
