ABSTRACT: Sodium absorption by the intestine is mediated by brush border Na+/H+ exchangers, which include the NHE3 and NHE8 isoforms. We demonstrated a maturational decrease in NHE8 and increase in NHE3 in mouse intestine mRNA abundance and brush border membrane protein abundance, indicating a developmental switch of isoforms. Congenital sodium diarrhea is a rare autosomal recessive disorder characterized by polyhydramnios, hyponatremia, metabolic acidosis, and diarrhea with a high sodium content. Previous studies using intestinal brush border membrane vesicles from patients with this disorder have demonstrated a decrease in Na+/H+ exchanger activity. Because some patients with congenital sodium diarrhea improve with age and knowing the developmental switch from NHE8 to NHE3, NHE8 may be a candidate gene for this disorder. We sequenced NHE8 from 5 patients with this disorder and found no disease-causing homozygous mutations. Although brush border membrane Na+/H+ exchange activity may be decreased, exonic mutations in NHE8 cannot account for this disorder in these subjects.
*Department of Pediatrics
†Department of Internal Medicine
‡Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Mattel Children's Hospital, David Geffen School of Medicine at the University of California, Los Angeles
§University of Birmingham Medical School, Birmingham, UK
||Department of Pediatrics, University of Helsinki, Helsinki, Finland.
Address correspondence and reprint requests to Michel Baum, MD, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9063 (e-mail: Michel.Baum@UTSouthwestern.edu).
Received 3 January, 2011
Accepted 2 May, 2011
This work was supported by NIH grants DK41612 (M.B. and O.W.M.), DK078596 (M.B.), DK083762 (M.G.M.), T32 DK07257, and the O’Brien Center P30DK079328.
The authors report no conflicts of interest.