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

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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 border2–4. 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.

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Turk, E., Zabel, B., Mundlos, S. et al. Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature 350, 354–356 (1991) doi:10.1038/350354a0

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