Glucose-galactose Malabsorption - Genetics

Genetics

The SLC5A1 gene provides instructions for producing a sodium/glucose cotransporter protein called SGLT1. This protein is found mainly in the intestinal tract and, to a lesser extent, in the kidneys, where it is involved in transporting glucose and the structurally similar galactose across cell membranes. The sodium/glucose cotransporter protein is important in the functioning of intestinal epithelial cells, which are cells that line the walls of the intestine. These cells have fingerlike projections called microvilli that absorb nutrients from food as it passes through the intestine. Based on their appearance, groups of these microvilli are known collectively as the brush border. The sodium/glucose cotransporter protein is involved in the process of glucose uptake in the instesinal cells due to a sodium gradient across the membrane. This is a secondary active transport because the sodium gradient generated for the functioning of the sodium/calcium exchanger is created by the sodium/potasium pump which requires ATP. Sodium and water are transported across the brush border along with the sugars in this process.

Mutations that prevent the sodium/glucose cotransporter protein from performing this function result in a buildup of glucose and galactose in the intestinal tract. This failure of active transport prevents the glucose and galactose from being absorbed and providing nourishment to the body. In addition, the water that normally would have been transported across the brush border with the sugar instead remains in the intestinal tract to be expelled with the stool, resulting in dehydration of the body's tissues and severe diarrhea.

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder. In some cases, individuals with one altered gene have reduced levels of glucose absorption capacity as measured in laboratory tests, but this has not generally been shown to have significant health effects.