title: Rare mutation in the SLC26A3 transporter causes life-long diarrhoea with metabolic alkalosis.
abstract: SLC26A3, a chloride/bicarbonate transporter mainly expressed in the intestines, plays a pivotal role in chloride absorption. We present a 23-year-old woman with a history of congenital chloride diarrhoea (CCD) and renal transplant who was admitted for rehydration and treatment of acute kidney injury after she presented with an acute diarrhoeal episode. Laboratory investigations confirmed metabolic alkalosis and severe hypochloraemia, consistent with her underlying CCD. This contrasts with most other forms of diarrhoea, which are normally associated with metabolic acidosis. Genetic testing was offered and revealed a homozygous non-sense mutation in SLC26A3 (Gly-187-Stop). This loss-of-function mutation results in bicarbonate retention in the blood and chloride loss into the intestinal lumen. Symptomatic management with daily NaCl and KCl oral syrups was supplemented with omeprazole therapy. The loss of her own kidneys is most likely due to crystal-induced nephropathy secondary to chronic volume contraction and chloride depletion. This case summarises the pathophysiology and management of CCD.
authors.affiliation: Yale Waterbury Internal Medicine Residency Program, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Maen D
authors.initials: MD
authors.lastname: Abou Ziki
authors.affiliation: Department of Medical Education, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Mohamud A
authors.initials: MA
authors.lastname: Verjee
mesh_terms: D000328:Adult; D000471:Alkalosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D001639:Bicarbonates / Q000097:blood; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics*; D002712:Chlorides / Q000378:metabolism* / Q000627:therapeutic use; D003967:Diarrhea / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000601:surgery; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D016030:Kidney Transplantation; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D009853:Omeprazole / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D054328:Proton Pump Inhibitors; C081011:SLC26A3 protein, human; D000076988:Sulfate Transporters; D009853:Omeprazole