Abstract：
Iron-refractory iron deficiency anaemia (IRIDA) is a rare autosomal recessive disorder, distinguished by hypochromic microcytic anaemia, low transferrin levels and inappropriately elevated hepcidin (HEPC) levels. It is caused by mutations in TMPRSS6 gene. Systematic screening of 500 pregnant women with iron deficiency anaemia having moderate to severe microcytosis with no other causes of anaemia were enrolled to rule out oral iron refractoriness. It identified a final cohort of 10 (2.15% prevalence) individuals with IRIDA phenotype. Haematological and biochemical analysis revealed significant differences between iron responders and iron non-responders, with iron non-responders showing lower haemoglobin, red blood cell count, serum iron and serum ferritin levels, along with elevated HEPC (9.47 ± 2.75 ng/mL, p = 0.0009) and erythropoietin (4.58 ± 4.07 µ/mL, p = 0.0196) levels. Genetic sequencing of the TMPRSS6 gene in this final cohort identified 10 novel variants, including seven missense and three frame-shift mutations, with four missense variants showing high functional impact defining the IRIDA phenotype. Structural analysis revealed significant damage caused by two variants (p.L83R and p.S235R). This study provides valuable insights into IRIDA among pregnant women in the Indian subcontinent, unveiling its underlying causes of unresponsiveness, genetic mechanisms and prevalence. Furthermore, research collaboration is essential to validate these findings and develop effective treatments.
摘要：
铁难治性缺铁性贫血（IRIDA）是一种罕见的常染色体隐性遗传疾病，以低色素性小细胞性贫血为特征，低转铁蛋白水平和铁调素（HEPC）水平不适当升高。它是由TMPRSS6基因突变引起的。对500名患有缺铁性贫血的孕妇进行了系统筛查，这些孕妇患有中度至重度微细胞增多症，没有其他贫血原因，以排除口服铁难治性。它确定了10名(2.15%患病率)具有IRIDA表型的个体的最终队列。血液和生化分析显示铁反应者和铁无反应者之间存在显着差异。铁无反应者显示血红蛋白较低，红细胞计数,血清铁和血清铁蛋白水平，随着HEPC升高（9.47±2.75ng/mL，p=0.0009）和促红细胞生成素（4.58±4.07µ/mL，p=0.0196）水平。TMPRSS6基因的基因测序在这个最后的队列中确定了10个新的变异，包括七个错义和三个移码突变，四个错义变体显示出高功能影响，定义了IRIDA表型。结构分析显示两个变体（p。L83R和p.S235R）。这项研究为印度次大陆孕妇的IRIDA提供了有价值的见解，揭示了其反应迟钝的根本原因，遗传机制和流行。此外，研究合作对于验证这些发现和开发有效的治疗方法至关重要.
