Marchesani Silvio, Di Mauro Margherita, Ceglie Giulia, Grassia Ginevra, Carletti Michaela, Cristofaro Rosa Carmela, Cossutta Matilde, Curcio Cristina, Palumbo Giuseppe
University Department of Pediatrics, Bambino Gesù Children's Hospital, University of Rome Tor Vergata, Rome, Italy.
Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Front Pediatr. 2023 Oct 6;11:1228443. doi: 10.3389/fped.2023.1228443. eCollection 2023.
Approximately 7% of the worldwide population exhibits variations in the globin genes. The recent migration of populations from countries where hemoglobin disorders are endemic has resulted in important epidemiological changes with the diffusion of newly discovered or poorly characterized genetic variants and new combinations and very heterogeneous clinical phenotypes. The aim of our study is to assess the parameters that are more significant in predicting a positive genetic testing outcome for hemoglobinopathies in a pediatric population of patients presenting with anemia or microcythemia, without a definite diagnosis.
This study included patients evaluated in our hematological outpatient clinic for anemia and/or microcythemia despite normal ferritin levels. A screening of pathological hemoglobins using high-performance liquid chromatography (HPLC) was performed for the entire population of the study. Subsequently, patients with hemoglobin (Hb) S trait and patients with an HPLC profile compatible with beta thalassemia trait were excluded from the study. Genetic screening tests for hemoglobinopathies were performed on the remaining patients, which involved measuring the red blood cell (RBC) counts, red blood cells distribution width (RDW), reticulocyte count, and mean corpuscular volume of reticulocytes (MCVr).
This study evaluated a total of 65 patients, consisting of nine patients with negative genetic analysis results and 56 patients with positive genetic analysis results. The Hb and RDW values in these two groups did not demonstrate statistical significance. On the other hand, there were statistically significant differences observed in the mean corpuscular volume (MCV), RBC count, reticulocyte count, and MCVr between the two groups. Furthermore, in the group of patients with positive genetic test results, specific genetic findings associated with different HPLC results were observed. In particular, 13 patients with positive genetic test results had normal HPLC findings.
This study has demonstrated that HPLC, while serving as a valuable first-level test, has some limitations. Specifically, it has been observed that some patients may exhibit a negative HPLC result despite a positive genetic analysis. In addition to the presence of low levels of Hb and HPLC alterations, other parameters could potentially indicate the underlying mutations in the globin genes. Therefore, we propose that the complete blood cell count be utilized as a widely available parameter for conducting targeted genetic analyses to avoid the risk of overlooking rare hemoglobinopathies.
全球约7%的人口存在珠蛋白基因变异。近期，来自血红蛋白疾病流行国家的人群迁移，导致了重要的流行病学变化，新发现的或特征不明的基因变异以及新的组合得以传播，临床表型也非常多样化。我们研究的目的是评估在未明确诊断的贫血或小红细胞血症儿科患者群体中，对血红蛋白病基因检测阳性结果预测更具意义的参数。
本研究纳入了在我们血液科门诊接受评估的贫血和/或小红细胞血症患者，尽管其铁蛋白水平正常。对研究的所有患者进行了高效液相色谱法（HPLC）检测病理性血红蛋白。随后，将具有血红蛋白（Hb）S性状的患者和HPLC图谱与β地中海贫血性状相符的患者排除在研究之外。对其余患者进行了血红蛋白病的基因筛查检测，包括测量红细胞（RBC）计数、红细胞分布宽度（RDW）、网织红细胞计数和网织红细胞平均体积（MCVr）。
本研究共评估了65例患者，其中9例基因分析结果为阴性，56例基因分析结果为阳性。这两组的Hb和RDW值无统计学意义。另一方面，两组之间的平均红细胞体积（MCV）、RBC计数、网织红细胞计数和MCVr存在统计学显著差异。此外，在基因检测结果为阳性的患者组中，观察到了与不同HPLC结果相关的特定基因发现。特别是，13例基因检测结果为阳性的患者HPLC结果正常。
本研究表明，HPLC虽然是一项有价值的一级检测，但存在一些局限性。具体而言，已观察到一些患者尽管基因分析为阳性，但HPLC结果可能为阴性。除了低水平Hb和HPLC改变的存在外，其他参数可能潜在地表明珠蛋白基因中的潜在突变。因此，我们建议将全血细胞计数作为进行靶向基因分析的广泛可用参数，以避免遗漏罕见血红蛋白病的风险。
