Objectives: Autosomal recessive, congenital chloride diarrhea (CLD) is a form of persistent secretory diarrhea, presenting with polyhydramnios and intractable diarrhea from birth. CLD is caused by mutations in the SLC26A3 gene, encoding a Na+-independent Cl−/HCO3- exchanger. The diagnosis is generally made on the basis of high fecal chloride concentration in patients with serum electrolyte homoeostasis corrected by salt substitution. We aimed to evaluate the role of diagnostic genetic testing in CLD.
Patients and Methods: Clinical and laboratory data were collected from 8 unrelated children diagnosed as having or suspected to have CLD. The evaluation included physical examination, routine clinical chemistry, and SLC26A3 mutation analysis by direct sequencing of DNA extracted from buccal swabs or peripheral leukocytes.
Results: CLD was initially diagnosed on high fecal chloride concentrations in 7 patients, and by mutation analysis in 1 patient. In 3 of these patients the correct diagnosis was made more than 6 months after birth. We identified SLC26A3 mutations on both alleles in all 8 patients with CLD, including 3 novel missense and 4 novel truncating mutations. We present a compilation of reported SLC26A3 mutations and polymorphisms.
Conclusions: The diagnosis and therapy of CLD were considerably delayed in 3 of 8 patients from this series, highlighting the potential of misdiagnosing CLD. We add 7 novel mutations, including 3 missense changes of highly conserved residues to a total of 41 mutations in this gene.
Molecular analysis is efficient and should be considered as a means of early diagnosis of CLD, especially if the clinical diagnosis remains uncertain.
*Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria
†Université Paris Descartes, Faculté Necker, INSERM U989, Paris, France
‡Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia
§Centre for Pediatric and Adolescent Medicine, Freiburg University Hospital, Freiburg, Germany
||Department of Pediatrics, Medical University of Vienna, Vienna, Austria
¶Deaconry Hospital, Schwaebisch Hall, Germany
#Centre for Paediatric Gastroenterology, UCL Medical School, Royal Free Campus, London, UK
**Royal Children's Hospital, Department of Gastroenterology, Herston, Australia
††Department of Pediatric Nephrology, Charité, Berlin, Germany
‡‡Department of Pediatrics II, Innsbruck Medical University, Innsbruck, Austria.
Received 7 September, 2010
Accepted 15 December, 2010
Address correspondence and reprint requests to Andreas R. Janecke, MD, Department of Pediatrics II, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria (e-mail: Andreas.Janecke@i-med.ac.at).
The present study was funded in part by Tiroler Medizinischer Forschungsfond (grant no. 198 to ARJ).
The authors report no conflicts of interest.