Ken-Ichiro Konishi1, Tatsuki Mizuochi2, Tadahiro Yanagi3, Yoriko Watanabe3, Kazuhiro Ohkubo4, Shouichi Ohga4, Hidehiko Maruyama5, Ichiro Takeuchi6, Yuji Sekine7, Kei Masuda8, Nobuyuki Kikuchi9, Yuka Yotsumoto10, Yasufumi Ohtsuka11, Hidenori Tanaka12, Takahiro Kudo13, Atsuko Noguchi14, Kazumasa Fuwa15, Sotaro Mushiake16, Shinobu Ida17, Jun Fujishiro18, Yushiro Yamashita3, Tomoaki Taguchi19, Ken Yamamoto20. 1. 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. 2. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. Electronic address: mizuochi_tatsuki@kurume-u.ac.jp. 3. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. 4. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 5. Division of Neonatology, National Center for Child Health and Development, Tokyo, Japan. 6. Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan. 7. Department of Emergency and General Medicine, Shizuoka Children's Hospital, Shizuoka, Japan. 8. Department of Pediatrics, Doai Memorial Hospital, Tokyo, Japan. 9. Department of Pediatrics, Yokohama City Minato Red Cross Hospital, Yokohama, Japan. 10. Department of Pediatrics, Takatsuki General Hospital, Takatsuki, Japan. 11. Department of Pediatrics, Saga University, Saga, Japan. 12. Department of Pediatrics, Komaki City Hospital, Komaki, Japan. 13. Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan. 14. Department of Pediatrics, Akita University Graduate School of Medicine, Akita, Japan. 15. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan. 16. Department of Pediatrics, Nara Hospital Kinki University, Ikoma, Japan. 17. Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan. 18. Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 19. Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 20. Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan.
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.
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.