Niss Omar, Lorsbach Robert B, Berger Mikaela, Chonat Satheesh, McLemore Morgan, Buchbinder David, McCavit Timothy, Shaffer Linda G, Simpson Jessica, Schwartz Jeffrey H, Meznarich Jessica, Emberesh Myesa, Seu Katie G, Zhang Wenying, Kalfa Theodosia A
Division of Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Blood Cells Mol Dis. 2021 Mar;87:102534. doi: 10.1016/j.bcmd.2020.102534. Epub 2020 Dec 24.
Congenital dyserythropoietic anemias (CDAs) are characterized by ineffective erythropoiesis and distinctive erythroblast abnormalities; the diagnosis is often missed or delayed due to significant phenotypic heterogeneity. We established the CDA Registry of North America (CDAR) to study the natural history of CDA and create a biorepository to investigate the pathobiology of this heterogeneous disease. Seven of 47 patients enrolled so far in CDAR have CDA-I due to biallelic CDAN1 mutations. They all presented with perinatal anemia and required transfusions during infancy. Anemia spontaneously improved during infancy in three patients; two became transfusion-independent rapidly after starting interferon-α; and two remain transfusion-dependent at last follow-up at ages 5 and 30 y.o. One of the transfusion-dependent patients underwent splenectomy at 11 y.o due to misdiagnosis and returned to medical attention at 27 y.o with severe hemolytic anemia and pulmonary hypertension. All patients developed iron overload even without transfusions; four were treated with chelation. Genetic testing allowed for more rapid and accurate diagnosis; the median age of confirmed diagnosis in our cohort was 3 y.o compared to 17.3 y.o historically. In conclusion, CDAR provides an organized research network for multidisciplinary clinical and research collaboration to conduct natural history and biologic studies in CDA.
先天性红细胞生成异常性贫血（CDA）的特征是红细胞生成无效和独特的成红细胞异常；由于显著的表型异质性，诊断常常被漏诊或延误。我们建立了北美CDA注册中心（CDAR），以研究CDA的自然病史，并创建一个生物样本库来研究这种异质性疾病的病理生物学。到目前为止，CDAR登记的47例患者中有7例因双等位基因CDAN1突变而患有CDA-I。他们均在围产期出现贫血，婴儿期需要输血。3例患者在婴儿期贫血自发改善；2例在开始使用α干扰素后迅速不再依赖输血；2例在5岁和30岁的最后一次随访时仍依赖输血。其中1例依赖输血的患者因误诊在11岁时接受了脾切除术，27岁时因严重溶血性贫血和肺动脉高压再次就医。所有患者即使未输血也出现了铁过载；4例接受了螯合治疗。基因检测实现了更快速、准确的诊断；我们队列中确诊的中位年龄为3岁，而历史上为17.3岁。总之，CDAR为多学科临床和研究合作提供了一个有组织的研究网络，以开展CDA的自然病史和生物学研究。
