Faculty of Medicine, Ihsan Dogramaci Childrens Hospital, Hacettepe University, Ankara, Turkey.
Department of Pediatrics, Division of Immunology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
J Clin Immunol. 2024 Nov 5;45(1):38. doi: 10.1007/s10875-024-01816-4.
Chronic neutropenia causes involve nutritional deficiencies and inborn errors of immunity(IEI), such as severe congenital neutropenia. To classify common chronic neutropenia causes in a pediatric immunology unit. We enrolled 109 chronic neutropenia patients admitted to a pediatric immunology department between 2002-2022. We recorded clinical/laboratory features and genetic characteristics. The male/female ratio was 63/46. Fifty-eight patients had parental consanguinity(57.4%). 26.6% (n = 29) patients had at least one individual in their family with neutropenia. Common symtpoms at presentation were upper respiratory tract infections(URTI)(31.1%), oral aphthae(23.6%), skin infections(23.6%), pneumonia(20.8%), and recurrent abscesses(12.3%). Common infections during follow-up were URTI(56.8%), pneumonia(33%), skin infections(25.6%), gastroenteritis(18.3%), and recurrent abscesses(14,6%). Common long-term complications were dental problems(n = 51), osteoporosis(n = 22), growth retardation(n = 14), malignancy(n = 16)[myelodysplastic syndrome(n = 10), large granulocytic leukemia(n = 1), acute lymphoblastic leukemia(n = 1), Hodgkin lymphoma(n = 1), EBV-related lymphoma(n = 1), leiomyosarcoma(n = 1), and thyroid neoplasm(n = 1)]. We performed a genetic study in 86 patients, and 69(71%) got a genetic diagnosis. Common gene defects were HAX-1(n = 26), ELA-2 (ELANE)(n = 10), AP3B1(n = 4), and ADA-2(n = 4) gene defects. The IEI ratio(70.6%) was high. GCSF treatment(93.4%), immunoglobulin replacement therapy(18.7%), and HSCT(15.9%) were the treatment options. The mortality rate was 12.9%(n = 14). The most common long term complications were dental problems that is three times more common in patients with known genetic mutations. We prepared an algorithm for chronic neutropenia depending on the present cohort. An important rate of inborn errors of immunity, especially combined immunodeficiency(11.9%) was presented in addition to congenital phagocytic cell defects. Early diagnosis will allow us tailor the disease-specific treatment options sooner, preventing irreversible consequences.
慢性中性粒细胞减少症的病因涉及营养缺乏和先天性免疫缺陷（IEI），例如严重的先天性中性粒细胞减少症。为了在儿科免疫学部门对常见的慢性中性粒细胞减少症的病因进行分类。我们招募了 2002 年至 2022 年间在儿科免疫学系就诊的 109 名慢性中性粒细胞减少症患者。我们记录了临床/实验室特征和遗传特征。男女比例为 63/46。58 名患者的父母有近亲结婚（57.4%）。26.6%（n=29）的患者家中至少有一名中性粒细胞减少症患者。就诊时常见的症状是上呼吸道感染（URTI）（31.1%）、口腔阿弗他溃疡（23.6%）、皮肤感染（23.6%）、肺炎（20.8%）和复发性脓肿（12.3%）。随访期间常见的感染是 URTI（56.8%）、肺炎（33%）、皮肤感染（25.6%）、胃肠炎（18.3%）和复发性脓肿（14.6%）。常见的长期并发症是牙齿问题（n=51）、骨质疏松症（n=22）、生长迟缓（n=14）、恶性肿瘤（n=16）[骨髓增生异常综合征（n=10）、大颗粒淋巴细胞白血病（n=1）、急性淋巴细胞白血病（n=1）、霍奇金淋巴瘤（n=1）、EBV 相关淋巴瘤（n=1）、平滑肌肉瘤（n=1）和甲状腺肿瘤（n=1）]。我们对 86 名患者进行了基因研究，其中 69 名（71%）获得了基因诊断。常见的基因缺陷是 HAX-1（n=26）、ELA-2（ELANE）（n=10）、AP3B1（n=4）和 ADA-2（n=4）基因缺陷。IEI 的比例（70.6%）很高。GCSF 治疗（93.4%）、免疫球蛋白替代治疗（18.7%）和 HSCT（15.9%）是治疗选择。死亡率为 12.9%（n=14）。最常见的长期并发症是牙齿问题，在已知基因突变的患者中，牙齿问题的发生率是三倍。我们根据本队列制定了慢性中性粒细胞减少症的算法。除了先天性吞噬细胞缺陷外，还存在免疫缺陷（11.9%）等先天性免疫缺陷。早期诊断将使我们能够更早地选择针对疾病的治疗方案，从而预防不可逆转的后果。
