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 journalArticle

Abstract

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
Volume214
DOIs
Publication statusPublished - Nov 2019

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Molecular Biology
Japan
Mutation
Far East
Congenital chloride diarrhea
Newborn Infant
Pediatrics

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

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Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea : A Nationwide Study in Japan. / Konishi, Ken ichiro; Mizuochi, Tatsuki; Yanagi, Tadahiro; Watanabe, Yoriko; Ohkubo, Kazuhiro; Ohga, Shouichi; Maruyama, Hidehiko; Takeuchi, Ichiro; Sekine, Yuji; Masuda, Kei; Kikuchi, Nobuyuki; Yotsumoto, Yuka; Ohtsuka, Yasufumi; Tanaka, Hidenori; Kudo, Takahiro; Noguchi, Atsuko; Fuwa, Kazumasa; Mushiake, Sotaro; Ida, Shinobu; Fujishiro, Jun; Yamashita, Yushiro; Taguchi, Tomoaki; Yamamoto, Ken.

In: Journal of Pediatrics, Vol. 214, 11.2019, p. 151-157.e6.

Research output: Contribution to journalArticle

Konishi, KI, Mizuochi, T, Yanagi, T, Watanabe, Y, Ohkubo, K, Ohga, S, Maruyama, H, Takeuchi, I, Sekine, Y, Masuda, K, Kikuchi, N, Yotsumoto, Y, Ohtsuka, Y, Tanaka, H, Kudo, T, Noguchi, A, Fuwa, K, Mushiake, S, Ida, S, Fujishiro, J, Yamashita, Y, Taguchi, T & Yamamoto, K 2019, 'Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan', Journal of Pediatrics, vol. 214, pp. 151-157.e6. https://doi.org/10.1016/j.jpeds.2019.07.039
Konishi, Ken ichiro ; Mizuochi, Tatsuki ; Yanagi, Tadahiro ; Watanabe, Yoriko ; Ohkubo, Kazuhiro ; Ohga, Shouichi ; Maruyama, Hidehiko ; Takeuchi, Ichiro ; Sekine, Yuji ; Masuda, Kei ; Kikuchi, Nobuyuki ; Yotsumoto, Yuka ; Ohtsuka, Yasufumi ; Tanaka, Hidenori ; Kudo, Takahiro ; Noguchi, Atsuko ; Fuwa, Kazumasa ; Mushiake, Sotaro ; Ida, Shinobu ; Fujishiro, Jun ; Yamashita, Yushiro ; Taguchi, Tomoaki ; Yamamoto, Ken. / Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea : A Nationwide Study in Japan. In: Journal of Pediatrics. 2019 ; Vol. 214. pp. 151-157.e6.
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abstract = "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.",
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AU - Konishi, Ken ichiro

AU - Mizuochi, Tatsuki

AU - Yanagi, Tadahiro

AU - Watanabe, Yoriko

AU - Ohkubo, Kazuhiro

AU - Ohga, Shouichi

AU - Maruyama, Hidehiko

AU - Takeuchi, Ichiro

AU - Sekine, Yuji

AU - Masuda, Kei

AU - Kikuchi, Nobuyuki

AU - Yotsumoto, Yuka

AU - Ohtsuka, Yasufumi

AU - Tanaka, Hidenori

AU - Kudo, Takahiro

AU - Noguchi, Atsuko

AU - Fuwa, Kazumasa

AU - Mushiake, Sotaro

AU - Ida, Shinobu

AU - Fujishiro, Jun

AU - Yamashita, Yushiro

AU - Taguchi, Tomoaki

AU - Yamamoto, Ken

PY - 2019/11

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N2 - 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.

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