A Novel Homozygous SLC26A3 Nonsense Mutation in a Tyrolean Girl With Congenital Chloride Diarrhea

摘要

Congenital chloride diarrhea (CLD) often manifests itself in utero when ultrasonography shows vastly distended fluid-filled fetal bowel loops and polyhydramnios (1). Postnatally, voluminous watery acidic stools with high chloride content cause hypochloremia, hyponatremia,hypokalemia, metabolic alkalosis, and dehydration. Additional characteristic clinical sequelae are abdominal distension, hyperbilirubinemia, and failure to thrive (2). The diagnosis can be verified by analyzing fecal electrolytes, which always show Cl~- concentrations above 90 mmol/L provided that body electrolyte balance has been corrected to normal.Pathophysiologically, a defect of ileal and colonic apical Cl~-/HCO_3~- exchange, normally providing absorption of Cl~- and secretion of HCO_3~-, has been found to be responsible for the disease (3). The protein involved in Cl~-/HCO_3~- exchange has been reported to be defective in CLD because of mutations in the SLC26A3 gene, also named the CLD- or downregulated in adenoma (DRA-) gene (4). Since this first description, approximately 30 mutations have been identified in patients with CLD from various countries all over the world (5).Here we describe a novel mutation associated with CLD in a female patient, who is the first person of Tyrolean heritage reported to be afflicted by this type of hereditary diarrhea.