Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan; Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
J Pediatr. 2019 Nov;214:151-157.e6. doi: 10.1016/j.jpeds.2019.07.039. Epub 2019 Aug 30.
To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD).
This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing.
Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation.
Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.
阐明日本先天性氯性腹泻（CCD）患儿的临床和遗传特征。
这是一项针对日本 616 家儿科中心的多机构、回顾性调查，在 2014 年至 2018 年间发现了 CCD 患者。通过 Sanger 测序检测 SLC26A3 相关突变。
13 名患者符合包括 SLC26A3 突变在内的所有纳入标准，14 名患者符合临床诊断标准。14 名患者中的 13 名（93%）存在 SLC26A3 中的纯合子或复合杂合突变，包括 6 种新突变。最常见的突变（13 例中有 7 例）为 c.2063-1g>t。诊断时的中位年龄为 1 天。符合所有标准的 9 名患者被诊断为新生儿（69%）。中位随访时间为 10 年。当研究时，8 名患者每天排便次数<5 次（62%），且排便次数均少于婴儿期。仅有 1 名患者存在肾钙质沉着症，3 名（23%）患者存在轻度慢性肾脏病。神经发育通常良好；仅有 1 名患者需要特殊教育。5 名患者（38%）接受了长期钠、钾和氯补充治疗。
早期胎儿超声诊断和及时的长期钠、钾和氯补充治疗是常见的治疗特征。SLC26A3 的基因分析提供了 CCD 的明确诊断。与之前报道的地区不同，c.2063-1g>t 可能是东亚的一个奠基突变。
