硫酸羟氯喹治疗肺表面活性蛋白C基因突变致婴儿间质性肺病1例并文献复习

目的：报道硫酸羟氯喹治疗肺表面活性蛋白C基因（SFTPC）突变致婴儿间质性肺病的疗效，提高对该病诊断和治疗的认识。方法：总结分析1例SFTPC突变致婴儿间质性肺病的临床特点、诊断过程和硫酸羟氯喹的疗效，并进行文献复习。结果：患儿女，2月龄，因“生后反复咳嗽伴气促2个月”于2015年9月9日就诊。患儿在新生儿期即发生呼吸窘迫，持续无法离氧。影像学示肺部渗出，病原学检查均阴性，常规抗感染治疗无效，否认肺部疾病家族史。基因检测发现SFTPC基因外显子4有1个杂合错义突变位点（c.T337C:p.Y113H），目前尚无报道。患儿13月龄时开始硫酸羟氯喹治疗，治疗6个月后，呼吸窘迫、生长发育情况和胸部CT影像学表现明显改善。在PubMed、Web of Science、中国知网、维普数据库和万方数据库中检索SFTPC基因突变的间质性肺病，检索时间均从建库至2016年12月1日，共检索到相关文献12篇，均为英文文献。总结包括本文1例患儿在内的51例SFTPC基因突变致间质性肺病病例使用硫酸羟氯喹的治疗情况，随访0.3~15.8年，其中单用硫酸羟氯喹治疗的有12例，均取得良好疗效，未提及或未发现药物不良反应；全身糖皮质激素合用硫酸羟氯喹治疗39例，33例（84.6%）有效，2例（5.1%）无改善，4例（10.3%）恶化（1例死亡）。结论：对于SFTPC基因突变的婴儿间质性肺病，早期发现和早期诊断很重要，及早使用硫酸羟氯喹治疗可以改善临床症状、体征和生长发育情况，减少终末肺的发生。

Hydroxychloroquine sulfate treatment for surfactant protein C gene mutation caused infantile interstitial lung disease and literature review

Objective To report the first case of hydroxychloroquine sulfate treatment for surfactant protein C gene(SFTPC)mutation caused infantile interstitial lung disease.Methods The clinical data,diagnostic process and curative effects of hydroxychloroquine sulfate in the treatment of surfactant protein C gene mutation with the infantile interstitial lung disease and related literatures were reviewed.Results A 2-months-old female baby,presented with coughing and shortness of breath for 2 months,was admitted to hospital on September 9th,2015.The case developed respiratory distress in neonatal period and required supplemental oxygen persistently.Imaging showed that there were lung shadows,various etiology examinations were negative,conventional anti infective therapy was ineffective,family history of pulmonary diseases was negative.A heterozygous missense SP-C mutation SFTPC(exon4):c.T337C,p.Y113H was identified which had not been reported yet.The patient was treated with hydroxychloroquine sulfate from 13 months of age.After 6 months treatment,respiratory distress,growth and chest CT were improved significantly.The retrieval of interstitial lung disease with mutations in the SFTPC gene was made in PubMed,Web of Science,Chinese CNKI,VIP database and Wanfang database.From the establishments of these databases to December 2016,a total of 12 articles were retrieved,all of them were foreign literatures.Including 1 case of this article,a total of 51 patients with SFTPC mutations which were treated by hydroxychloroquine sulfate were reported and followed up for 0.3-15.8 years.There were good effects in all 12 patients(100%),who were treated with hydroxychloroquine sulfate only,and without adverse drug reactions or no mentions.39 cases were treated with systemic corticosteroids combined with hydroxychloroquine sulfate.Among them,33 cases were improved(84.6％),2 cases(5.1％)not improved,4 cases(10.3％)deteriorated(1 case died).Conclusion Early detections and early diagnoses are very important for these SFTPC gene mutations in infants with interstitial lung diseases.Early treatment of hydroxychloroquine sulfate will be beneficial to improve the growth and development,clinical symptoms and signs,and reduce the incidence of end-stage lung.