Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan

Ken ichiro Konishi, Tatsuki Mizuochi, Tadahiro Yanagi, Yoriko Watanabe, Kazuhiro Ohkubo, Shouichi Ohga, Hidehiko Maruyama, Ichiro Takeuchi, Yuji Sekine, Kei Masuda, Nobuyuki Kikuchi, Yuka Yotsumoto, Yasufumi Ohtsuka, Hidenori Tanaka, Takahiro Kudo, Atsuko Noguchi, Kazumasa Fuwa, Sotaro Mushiake, Shinobu Ida, Jun FujishiroYushiro Yamashita, Tomoaki Taguchi, Ken Yamamoto

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Objective: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). Study design: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)151-157.e6
JournalJournal of Pediatrics
Publication statusPublished - Nov 2019

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health


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