Yang Tongyu, Zhang Feizhou, Zheng Guimei, Yang Dehua, Wu Lei, Jia Xuan, Zhu Guohong, Tang Lanfang
Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
National Clinical Research Center for Child Health, 3333 Binsheng Rd, Hangzhou, 310052, Zhejiang Province, China.
Ital J Pediatr. 2025 Sep 1;51(1):266. doi: 10.1186/s13052-025-02101-9.
In pulmonary surfactants, surfactant protein C (SP-C) plays a critical role in regulating surface tension at the air-liquid interface of alveoli, primarily due to its robust hydrophobic property. Genetic mutations in the SP-C gene can compromise its structural integrity, thereby impairing its functional efficiency in surface tension modulation.
A retrospective analysis was performed on 11 pediatric patients harboring SP-C gene mutations who were admitted to our medical center between June 2014 and June 2024.
11 pediatric patients with heterozygous SFTPC gene mutations were identified at our center. The age of onset spanned from birth to 5 years 2 months. Genetic analysis revealed that 9 patients carried the same SFTPC gene mutation at c.218T > C (p.Ile73Thr). 1 case previously reported, had compound mutations in both NKX2-1 and SFTPC genes. 1 case was newly identified splicing variant (c.612 + 1G > T). Predominant clinical manifestations included dyspnea and respiratory failure. Chest imaging predominantly demonstrates interstitial lung diseases (ILDs). In treatment, besides oxygen support, 3 patients received hydroxychloroquine (Hch) and 7 cases were administered azithromycin for infection prophylaxis. All patients received low-dose methylprednisolone (1-2 mg/kg/day) during the course. Bronchoalveolar lavage (BAL) was performed in 3 cases with pulmonary alveolar proteinosis and one cases with pulmonary atelectasis. Long-term follow-up through the present time revealed 4 deaths and 7 survivors among the cohort.
The c.218T > C (p.Ile73Thr) variant represents a hotspot mutation in the SFTPC gene, clinically manifesting as ILDs. The therapeutic efficacy of Hch in managing ILDs has been increasingly recognized in clinical practice. BAL is assuming a growing role in both the diagnosis and treatment of SFTPC-related pediatric ILD. Given the heterogeneity of mutation sites, the pathogenic mechanisms underlying lung injury may vary among patients, underscoring the need for personalized diagnostic and therapeutic strategies tailored to specific genetic profiles.
在肺表面活性剂中，表面活性蛋白C（SP-C）在调节肺泡气液界面的表面张力方面起着关键作用，这主要归因于其强大的疏水性。SP-C基因的基因突变会损害其结构完整性，从而削弱其在表面张力调节中的功能效率。
对2014年6月至2024年6月期间入住我院的11例携带SP-C基因突变的儿科患者进行回顾性分析。
在我院中心共鉴定出11例携带SFTPC基因杂合突变的儿科患者。发病年龄从出生到5岁2个月不等。基因分析显示，9例患者携带相同的SFTPC基因突变，即c.218T>C（p.Ile73Thr）。1例既往报道的病例在NKX2-1和SFTPC基因中均有复合突变。1例为新发现的剪接变体（c.612+1G>T）。主要临床表现为呼吸困难和呼吸衰竭。胸部影像学主要表现为间质性肺疾病（ILDs）。在治疗方面，除了氧疗支持外，3例患者接受了羟氯喹（Hch）治疗，7例患者使用阿奇霉素预防感染。所有患者在病程中均接受低剂量甲泼尼龙（1-2mg/kg/天）治疗。3例肺泡蛋白沉积症患者和1例肺不张患者进行了支气管肺泡灌洗（BAL）。截至目前的长期随访显示，该队列中有4例死亡，7例存活。
c.218T>C（p.Ile73Thr）变体是SFTPC基因中的一个热点突变，临床表现为ILDs。在临床实践中，Hch治疗ILDs的疗效已得到越来越多的认可。BAL在SFTPC相关儿科ILD的诊断和治疗中发挥着越来越重要的作用。鉴于突变位点的异质性，不同患者肺损伤的致病机制可能不同，这突出了针对特定基因谱制定个性化诊断和治疗策略的必要性。
