Glucose/galactose malabsorption caused by a defect in the Na⁺/glucose cotransporter

Abstract

GLUCOSE/galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life and characterized by a selective failure to absorb dietary glucose and galactose from the intestine¹. The consequent severe diarrhoea and dehydration are usually fatal unless these sugars are eliminated from the diet. Intestinal biopsies of GGM patients have revealed a specific defect in Na⁺-dependent absorption of glucose in the brush border^2–4. Normal glucose absorption is mediated by the Na⁺/glucose cotransporter in the brush border membrane of the intestinal epithelium⁵. Cellular influx is driven by the transmem-brane Na⁺ electrochemical potential gradient; thereafter the sugar moves to the blood across the basolateral membrane via the facilitated glucose carrier. We have previously cloned and sequenced a Na⁺/glucose cotransporter from normal human ileum⁶ and shown that this gene, SGLT1, resides on the distal q arm of chromosome 22⁷. We have now amplified SGLT1 complementary DNA and genomic DNA from members of a family affected with GGM by the polymerase chain reaction⁸. Sequence analysis of the amplified products has revealed a single missense mutation in SGLT1 which cosegregates with the GGM phenotype and results in a complete loss of Na⁺-dependent glucose transport in Xenopus oocytes injected with this complementary RNA.