Chen Xinying, Zhao Xiaoxin, Pan Bo, Wang Lianyu, Xie Wensi, Jiang Wenwen, Yang Jinghua, Wu Weixia, Li Yanxin
Department of Pediatrics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, No. 111 Dade Road, Yuexiu District, 510120, Guangzhou, China.
Xiaorong Luo's National Famous Expert Inheritance Studio, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
J Clin Immunol. 2025 Jul 12;45(1):113. doi: 10.1007/s10875-025-01905-y.
Congenital neutropenia (CN) is a rare hereditary blood disorder characterized by a significant reduction in neutrophils, making patients prone to recurrent and severe infections and even a risk of developing myelodysplastic syndrome or acute leukemia, often caused by the ELANE variants, and the complex relationship between ELANE variants and clinical phenotypes, as well as the natural course of the disease, remains unclear. We describe a case of CN in a Chinese infant caused by the De Novo missense variant c.170 C > A in the ELANE gene, presented with persistent neutropenia since the neonatal period, accompanied by recurrent infections. He did not receive G-CSF treatment due to the declination of his parents, but antibiotics were administered during infections or with high hsCRP levels. During the early neonatal stage, the patient consistently exhibited severe neutropenia (ANC < 0.5 × 10^9/L). Periodic fluctuations in neutrophil counts observed twice a week during particular months suggest a cyclical pattern. Until now, he still experiences varying degrees of neutropenia persistently, with ANC occasionally exceeding 1.0 × 10^9/L during infections. Multiple prediction scoring tools and models support the pathogenicity of this missense variant. This case highlights a rare pathogenic variant of ELANE, which, to our knowledge, is the first case of the variant c.170 C > A (p.Ala57Asp) of the intermediate phenotype of CN in mainland China and a rare variant globally, indicating phenotypic variability in ELANE-related neutropenia due to an Ala57 mutation. The clinical management of CN caused by ELANE variants poses a challenge for clinicians and deserves attention. Timely diagnosis, treatment, and extended follow-up are of paramount value.
先天性中性粒细胞减少症（CN）是一种罕见的遗传性血液疾病，其特征是中性粒细胞显著减少，使患者易于反复发生严重感染，甚至有发展为骨髓增生异常综合征或急性白血病的风险，该病通常由ELANE基因变异引起，而ELANE基因变异与临床表型之间的复杂关系以及疾病的自然病程仍不清楚。我们描述了一名中国婴儿患CN的病例，该病例由ELANE基因的新发错义变异c.170 C＞A引起，自新生儿期起就出现持续性中性粒细胞减少，并伴有反复感染。由于其父母拒绝，他未接受粒细胞集落刺激因子（G-CSF）治疗，但在感染期间或高敏C反应蛋白（hsCRP）水平升高时给予了抗生素治疗。在新生儿早期，该患者持续表现为严重中性粒细胞减少（绝对中性粒细胞计数[ANC]＜0.5×10^9/L）。在特定月份每周两次观察到的中性粒细胞计数的周期性波动提示存在周期性模式。截至目前，他仍持续存在不同程度的中性粒细胞减少，在感染期间ANC偶尔超过1.0×10^9/L。多种预测评分工具和模型支持这种错义变异的致病性。该病例突出了一种罕见的ELANE致病变异，据我们所知，这是中国大陆首例ELANE基因中间表型的c.170 C＞A（p.Ala57Asp）变异，在全球范围内也是一种罕见变异，表明由于丙氨酸57突变导致ELANE相关中性粒细胞减少症存在表型变异性。由ELANE基因变异引起的CN的临床管理对临床医生构成了挑战，值得关注。及时诊断、治疗和延长随访至关重要。
