Genotype-dependency of butyrate efficacy in children with congenital chloride diarrhea

Orphanet Journal of Rare Diseases

Giuseppe Castaldo²  Riccardo Troncone⁷  Antonio Calignano⁴  Rossella Tomaiuolo²  Felice Amato²  Chiara Centenari⁶  Annalisa Pedrolli⁶  Peter Heinz-Erian¹  Vincenza Pezzella³  Ausilia Elce²  Gianluca Terrin⁵  Roberto Berni Canani⁷ 

[1] Department of Pediatrics, Medical University, Innsbruck, Austria;Italy CEINGE–Biotecnologie Avanzate, Naples, Italy;Department of Translational Medical Science - Pediatric Section, and European Laboratory for the Investigation of Food Induced Diseases, University of Naples, “Federico II” Via S. Pansini, 5 80131 Naples, Italy;Department of Pharmacology, University of Naples, Federico II, Naples, Italy;Department of Gynecology-Obstetrics and Perinatal Medicine, University of Rome, “La Sapienza”, Rome, Italy;Department of Pediatrics, Trento Hospital, Trento, Italy;European Laboratory for the Investigation of Food Induced Diseases, University of Naples, Federico II, Naples, Italy

关键词: Children;    Pediatrics;    Short chain fatty acids;    Mutations;    DRA;    SLC26A6;    SLC26A3;   

Others  :  863352
DOI  :  10.1186/1750-1172-8-194

 received in 2013-06-04, accepted in 2013-12-10,  发布年份 2013

【 摘 要 】

Background

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by life-long, severe diarrhea with intestinal Cl^- malabsorption. It results from a reduced activity of the down regulated in adenoma exchanger (DRA), due to mutations in the solute carrier family 26, member 3 (SLC26A3) gene. Currently available therapies are not able to limit the severity of diarrhea in CLD. Conflicting results have been reported on the therapeutic efficacy of oral butyrate.

Methods

We investigated the effect of oral butyrate (100 mg/kg/day) in seven CLD children with different SLC26A3 genotypes. Nasal epithelial cells were obtained to assess the effect of butyrate on the expression of the two main Cl^- transporters: DRA and putative anion transporter-1 (PAT-1).

Results

A variable clinical response to butyrate was observed regarding the stool pattern and fecal ion loss. The best response was observed in subjects with missense and deletion mutations. Variable response to butyrate was also observed on SLC26A3 (DRA) and SLC26A6 (PAT1) gene expression in nasal epithelial cells of CLD patients.

Conclusions

We demonstrate a genotype-dependency for butyrate therapeutic efficacy in CLD. The effect of butyrate is related in part on a different modulation of the expression of the two main apical membrane Cl^- exchangers of epithelial cells, members of the SLC26 anion family.

Trial registration

Australian New Zealand Clinical trial Registry ACTRN12613000450718.

【 授权许可】

   
2013 Canani et al.; licensee BioMed Central Ltd.

【 图 表 】

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