Capra Anna Paola, Ferro Elisa, Cannavò Laura, La Rosa Maria Angela, Zirilli Giuseppina
a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , 'Gaetano Martino' University Hospital of Messina , Messina , Italy.
Hematology. 2017 Oct;22(9):559-564. doi: 10.1080/10245332.2017.1317990. Epub 2017 Apr 27.
We report a case of a 7-year-old girl with severe hypochromic microcytic anemia, who was unresponsive to classical iron supplements. We suspected IRIDA, iron-refractory iron-deficiency anemia, a genetic iron metabolism disorder, caused by TMPRSS6 variations. TMPRSS6 encodes matriptase-2, a negative regulator of hepcidin, and its pathological variants are related to normal to high levels of hepcidin. We analyzed the TMPRSS6 gene and we improved clinical management of the patient, selecting the appropriate supplementation therapy. Intervention & Technique: The parenteral iron therapy was started, but the patient was only partially responsive and the anemia persisted. To confirm the diagnosis, the TMPRSS6 gene sequence was analyzed by DNA sequencing and other relevant biochemical parameters were evaluated.
The TMPRSS6 sequence analysis showed a complex genotype with a rare heterozygous missense variant, in addition to other common polymorphisms. The serum hepcidin value was normal. We unexpectedly observed a normalization of patient's hemoglobin (Hb) levels only after liposomal iron treatment.
The proband was symptomatic for IRIDA during a critical phase of growth and development, but we did not find a clearly causative genotype. A long-term result, improving stably patient's Hb levels, was obtained only after liposomal iron supplementation. Children may be at greater risk for iron deficiency and the degree of anemia as well as the response to the iron supplements varies markedly patient to patient. Here, we show the importance of comprehensive study of these patients in order to collect useful information about genotype-phenotype association of genes involved in iron metabolism.
我们报告一例7岁重度低色素小细胞贫血女孩，她对传统铁剂补充无反应。我们怀疑是IRIDA，即铁难治性缺铁性贫血，一种由TMPRSS6变异引起的遗传性铁代谢紊乱疾病。TMPRSS6编码matriptase-2，一种铁调素的负调节因子，其病理变异与铁调素水平正常至高值有关。我们分析了TMPRSS6基因，并改善了患者的临床管理，选择了合适的补充治疗方法。干预与技术：开始进行胃肠外铁剂治疗，但患者仅部分有反应，贫血持续存在。为确诊，通过DNA测序分析了TMPRSS6基因序列，并评估了其他相关生化参数。
TMPRSS6序列分析显示除其他常见多态性外，还有一个罕见的杂合错义变异的复杂基因型。血清铁调素值正常。我们意外地发现，仅在脂质体铁治疗后患者的血红蛋白（Hb）水平恢复正常。
先证者在生长发育的关键阶段出现IRIDA症状，但我们未发现明确的致病基因型。仅在补充脂质体铁后才获得了稳定提高患者Hb水平的长期结果。儿童缺铁风险可能更高，贫血程度以及对铁剂补充的反应在患者之间差异显著。在此，我们展示了对这些患者进行全面研究的重要性，以便收集有关铁代谢相关基因的基因型-表型关联的有用信息。
