Glucose Galactose Malabsorption

The importance of human SGLT-1 for intestinal glucose absorption is exemplified in glucose-galactose malabsorption, a rare inborn error of glucose transport. This condition gives rise to a severe watery diarrhea in neonates, which is lethal unless glucose- and galactose-containing foods are removed from the diet. The diarrhea occurs because the unabsorbed hexoses enter the colon and are fermented into diarrheogenic compounds. The lack of hexose absorption in two sisters with the condition appears to be due to a single base change at nucleotide position 92, where a guanine is replaced by adenine. The mutation changed amino acid 28 of their SGLT-1 from aspartate to asparagine, making the SGLT-1 cotransporter defective and inactive. A single amino-acid alteration in the 664 that make up the molecule makes it unable to function as a cotransporter (43). Thus in humans who lack a functional SGLT-1, it appears that absorption of glucose and galactose cannot proceed normally. Experimental studies measuring the absorption of glucose in human jejunum in vivo showed that more than 95% of glucose absorption occurred by a carrier-mediated process, which agrees with the described pathophysiology of glucose-galactose malabsorption ( 44, 45).

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