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 language | English |
|---|---|
| Pages (from-to) | 151-157.e6 |
| Journal | Journal of Pediatrics |
| Volume | 214 |
| DOIs | |
| Publication status | Published - Nov 2019 |
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All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health
Cite this
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 journal › Article
}
TY - JOUR
T1 - Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea
T2 - A Nationwide Study in Japan
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
Y1 - 2019/11
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071425337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071425337&partnerID=8YFLogxK
U2 - 10.1016/j.jpeds.2019.07.039
DO - 10.1016/j.jpeds.2019.07.039
M3 - Article
C2 - 31477378
AN - SCOPUS:85071425337
VL - 214
SP - 151-157.e6
JO - Journal of Pediatrics
JF - Journal of Pediatrics
SN - 0022-3476
ER -