Congenital Dyserythropoietic Anemia type I (CDA I) is a rare hereditary condition characterized by macrocytic/normocytic anemia, splenomegaly, iron overload, and distinct abnormalities during late erythropoiesis, particularly internuclear bridges between erythroblasts. Diagnosis of CDA I remains challenging due to its rarity, clinical heterogeneity, and overlapping phenotype with other rare hereditary anemias. In this case series, we present 36 patients with suspected CDA I. A molecular diagnosis was successfully established in 89% of cases, identifying 16 patients with CDA I through the presence of 18 causative variants in the CDAN1 or CDIN1 genes. Transcriptomic analysis of CDIN1 variants revealed impaired erythroid differentiation and disruptions in transcription, cell proliferation, and histone regulation. Conversely, 16 individuals received a different diagnosis, primarily pyruvate kinase deficiency. Comparisons between CDA I and non‐CDA I patients revealed no significant differences in erythroblast morphological features. However, hemoglobin levels and red blood cell count differed between the two groups, with non‐CDA I subjects being more severely affected. Notably, most patients with severe anemia belonged to the non‐CDA I group (82% non‐CDA I vs. 18% CDA I), with a subsequent absolute prevalence of transfusion dependency among non‐CDA I patients (100% vs. 41.7%). All patients exhibited reduced bone marrow responsiveness to anemia, with a more pronounced effect observed in non‐CDA I patients. Erythropoietin levels were significantly higher in non‐CDA I patients compared to CDA I patients. However, evaluations of erythroferrone, soluble transferrin receptor, and hepcidin revealed no significant differences in plasma concentration between the two groups.

中文翻译：

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揭示疑似先天性红细胞生成障碍性贫血 I 型的遗传图谱：36 名患者的回顾性队列研究

先天性红细胞生成障碍性贫血 I 型 (CDA I) 是一种罕见的遗传性疾病，其特征是大红细胞/正红细胞贫血、脾肿大、铁超载以及晚期红细胞生成过程中的明显异常，特别是红细胞之间的核间桥。由于其罕见性、临床异质性以及与其他罕见遗传性贫血表型重叠，CDA I 的诊断仍然具有挑战性。在这个病例系列中，我们介绍了 36 名疑似 CDA I 患者。89% 的病例成功建立了分子诊断，通过基因组中存在 18 种致病变异，识别出 16 名 CDA I 患者。CDAN1或者CDIN1基因。转录组分析CDIN1变异揭示了红系分化受损以及转录、细胞增殖和组蛋白调节的破坏。相反，16 人得到了不同的诊断，主要是丙酮酸激酶缺乏症。 CDA I 和非 CDA I 患者之间的比较显示，成红细胞形态特征没有显着差异。然而，两组之间的血红蛋白水平和红细胞计数存在差异，非 CDA I 受试者受到的影响更为严重。值得注意的是，大多数严重贫血患者属于非 CDA I 组（82% 非 CDA I 组 vs. 18% CDA I），随后非 CDA I 组患者输血依赖的绝对患病率（100% vs. 41.7%） %）。所有患者均表现出骨髓对贫血的反应性降低，在非 CDA I 患者中观察到更明显的影响。与 CDA I 患者相比，非 CDA I 患者的促红细胞生成素水平显着较高。然而，对赤铁酮、可溶性转铁蛋白受体和铁调素的评估显示，两组之间的血浆浓度没有显着差异。