Neutropenia is a hematological condition characterized by a decrease in absolute neutrophil count (ANC) in peripheral blood, typically classified in adults as mild (1–1.5 × 10⁹/L), moderate (0.5–1 × 10⁹/L), or severe (< 0.5 × 10⁹/L). It can be categorized into two types: congenital and acquired. Congenital severe chronic neutropenia (SCN) arises from mutations in various genes, with different inheritance patterns, including autosomal recessive, autosomal dominant, and X-linked forms, often linked to mitochondrial diseases. The most common genetic cause is alterations in the ELANE gene. Some cases exist as non-syndromic neutropenia within the SCN spectrum, where genetic origins remain unidentified. The clinical consequences of congenital neutropenia depend on granulocyte levels and dysfunction. Infants with this condition often experience recurrent bacterial infections, with approximately half facing severe infections within their first six months of life. These infections commonly affect the respiratory system, digestive tract, and skin, resulting in symptoms like fever, abscesses, and even sepsis. The severity of these symptoms varies, and the specific organs and systems affected depend on the genetic defect. Congenital neutropenia elevates the risk of developing acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), particularly with certain genetic variants. SCN patients may acquire CSF3R and RUNX1 mutations, which can predict the development of leukemia. It is important to note that high-dose granulocyte colony-stimulating factor (G-CSF) treatment may have the potential to promote leukemogenesis. Treatment for neutropenia involves antibiotics, drugs that boost neutrophil production, or bone marrow transplants. Immediate treatment is essential due to the heightened risk of severe infections. In severe congenital or cyclic neutropenia (CyN), the primary therapy is G-CSF, often combined with antibiotics. The G-CSF dosage is gradually increased to normalize neutrophil counts. Hematopoietic stem cell transplants are considered for non-responders or those at risk of AML/MDS. In cases of WHIM syndrome, CXCR4 inhibitors can be effective. Future treatments may involve gene editing and the use of the diabetes drug empagliflozin to alleviate neutropenia symptoms.

中性粒细胞减少症是一种血液病，其特征是外周血中中性粒细胞绝对计数 (ANC) 减少，通常将成人分为轻度 (1–1.5 × 10 ⁹ /L)、中度 (0.5–1 × 10 ⁹ /L) 或严重（<0.5×10 ⁹ /L）。它可以分为两种类型：先天性和后天性。先天性严重慢性中性粒细胞减少症（SCN）由多种基因突变引起，具有不同的遗传模式，包括常染色体隐性遗传、常染色体显性遗传和X连锁形式，通常与线粒体疾病有关。最常见的遗传原因是ELANE基因的改变。有些病例存在 SCN 谱系内的非综合征性中性粒细胞减少症，其遗传起源仍未确定。先天性中性粒细胞减少症的临床后果取决于粒细胞水平和功能障碍。患有这种疾病的婴儿经常会经历反复的细菌感染，其中大约一半的婴儿在出生后的头六个月内面临严重感染。这些感染通常会影响呼吸系统、消化道和皮肤，导致发烧、脓肿甚至败血症等症状。这些症状的严重程度各不相同，受影响的具体器官和系统取决于遗传缺陷。先天性中性粒细胞减少症会增加患急性髓系白血病 (AML) 或骨髓增生异常综合征 (MDS) 的风险，特别是对于某些遗传变异。SCN患者可能会获得CSF3R和RUNX1突变，这可以预测白血病的发展。值得注意的是，高剂量粒细胞集落刺激因子（G-CSF）治疗可能有促进白血病发生的潜力。中性粒细胞减少症的治疗涉及抗生素、促进中性粒细胞产生的药物或骨髓移植。由于严重感染的风险增加，立即治疗至关重要。对于严重的先天性或周期性中性粒细胞减少症 (CyN)，主要治疗方法是 G-CSF，通常与抗生素联合使用。逐渐增加 G-CSF 剂量以使中性粒细胞计数正常化。对于无反应者或有 AML/MDS 风险的人，可考虑进行造血干细胞移植。对于 WHIM 综合征，CXCR4 抑制剂可能有效。未来的治疗可能涉及基因编辑和使用糖尿病药物恩格列净来缓解中性粒细胞减少症症状。