Significance of Molecular Testing for Congenital Chloride Diarrhea

Creators: Lechner, Silvia and Ruemmele, Frank and Zankl, Andreas and Lausch, Ekkehart and Huber, Wolf-Dietrich and Mihatsch, Walter and Phillips, Alan and Lewindon, Peter and Querfeld, Uwe and Heinz-Erian, Peter and Müller, Thomas and Janecke, Andreas
Title: Significance of Molecular Testing for Congenital Chloride Diarrhea
Item Type: Article or issue of a publication series
Journal or Series Title: Journal of Pediatric Gastroenterology and Nutrition : JPGN
Page Range: pp. 48-54
Date: 2011
Divisions: Gesundheitsmanagement
Abstract: 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. 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. 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. 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.
Forthcoming: No
Citation:

Lechner, Silvia and Ruemmele, Frank and Zankl, Andreas and Lausch, Ekkehart and Huber, Wolf-Dietrich and Mihatsch, Walter and Phillips, Alan and Lewindon, Peter and Querfeld, Uwe and Heinz-Erian, Peter and Müller, Thomas and Janecke, Andreas (2011) Significance of Molecular Testing for Congenital Chloride Diarrhea. Journal of Pediatric Gastroenterology and Nutrition : JPGN, 53. pp. 48-54. ISSN 0277-2116

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