Glucose-galactose malabsorption is a condition in which the body cannot take in (absorb) the sugars glucose and galactose, which primarily results in severe diarrhea. Beginning in infancy, severe diarrhea results in weight loss and dehydration that can be life-threatening. Small amounts of the simple sugar glucose in the urine (mild glucosuria) may occur in this disorder. Rarely, affected infants develop kidney stones due to deposits of calcium in the kidneys (nephrocalcinosis).

The signs and symptoms of glucose-galactose malabsorption appear early in life when affected infants are fed breast milk or regular infant formulas. These foods contain glucose, galactose, and another sugar called lactose that gets broken down into these two sugars. When these sugar-containing foods are ingested by affected individuals, it leads to diarrhea and other health problems. If foods that contain glucose, galactose, and lactose are removed from the diet, the diarrhea stops.

Mutations in the SLC5A1 gene cause glucose-galactose malabsorption. The SLC5A1 gene provides instructions for producing a protein called sodium/glucose cotransporter protein 1 (SGLT1). This protein is found mainly in the intestinal tract and the kidneys. It spans the membrane of cells in these body systems and moves (transports) glucose and galactose from outside the cell to inside the cell. Sodium and water are transported across the cell membrane along with the sugars in this process. Glucose and galactose are simple sugars; they are present in many foods, or they can be obtained from the breakdown of lactose or other sugars and carbohydrates in the diet during digestion.

In the intestinal tract, the SGLT1 protein helps the body absorb glucose and galactose from the diet so the body can use them. During the digestion of food, the protein transports the sugars into the cells that line the wall of the intestine (intestinal epithelial cells) as food passes through.

The SGLT1 protein in kidney cells plays a role in maintaining normal blood glucose levels. The kidneys filter waste products from the blood and eliminate them in urine. They also reabsorb needed nutrients and release them back into the blood. The SGLT1 protein transports glucose into specialized kidney cells, ensuring that the sugar goes back into the bloodstream and is not released into the urine.

SLC5A1 gene mutations impair or eliminate the function of the SGLT1 protein. As a result, glucose and galactose are not absorbed by intestinal epithelial cells but instead accumulate in the intestinal tract. In addition, water that normally would have been transported with the sugars remains in the intestinal tract, resulting in dehydration of the body's tissues and severe diarrhea. The SGLT1 protein in kidney cells cannot transport glucose; however, other proteins in the kidneys are able to absorb enough glucose into the bloodstream, so that glucosuria is mild, if present at all, in people with glucose-galactose malabsorption.

Normal Function

The SLC5A1 gene provides instructions for producing a protein called sodium/glucose cotransporter protein 1 (SGLT1). This protein is found mainly in the intestinal tract and the kidneys. It spans the membrane of cells and moves (transports) two sugars called glucose and galactose from outside the cell to inside the cell. Sodium and water are transported across the cell membrane along with the sugars in this process. Glucose and galactose are simple sugars; they are present in many foods, or they can be obtained from the breakdown of other sugars (such as lactose, the sugar found in milk) and carbohydrates in the diet during digestion.

In the intestinal tract, the SGLT1 protein helps take in (absorb) glucose and galactose from the diet. The protein is found in 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 SGLT1 protein is involved in the process of transporting glucose and galactose across the membrane of the intestinal epithelial cells so the sugars can be absorbed and used by the body.

The SGLT1 protein also plays a role in maintaining normal glucose levels in the body. In the kidneys, the SGLT1 protein is located in structures called proximal tubules. These structures help ensure that all nutrients have been extracted from waste fluids before the fluids are released from the body as urine. The SGLT1 protein, and a similar protein called SGLT2, transport glucose from proximal tubules, ensuring that the sugar is absorbed into the bloodstream and not released into the urine. The activity of the SGLT1 protein is the last step of glucose absorption in the kidneys.

Health Conditions Related to Genetic Changes

Glucose-galactose malabsorption

More than 60 mutations in the SLC5A1 gene have been found to cause glucose-galactose malabsorption. This condition begins in infancy and is characterized by severe diarrhea, resulting in weight loss and dehydration that can be life-threatening. SLC5A1 gene mutations impair or eliminate the function of the SGLT1 protein. Some mutations result in a protein that is folded into the incorrect shape, other mutations result in a protein that is abnormally short.

The altered SGLT1 protein's ability to transport glucose and galactose is reduced or absent. The sugars are not fully absorbed by intestinal epithelial cells, but instead accumulate in the intestinal tract. In addition, water that normally would have been transported with the sugars remains in the intestinal tract, resulting in dehydration of the body's tissues and severe diarrhea. In the kidneys, the SGLT1 protein cannot filter glucose; however, other proteins in the proximal tubules, including the SGLT2 protein, are able to absorb enough glucose into the bloodstream, so that glucose in the urine (glucosuria) is mild, if present at all, in people with glucose-galactose malabsorption.

Other Names for This Gene

• D22S675
• Human Na+/glucose cotransporter 1 mRNA, complete cds
• NAGT
• SC5A1_HUMAN
• SGLT1
• solute carrier family 5 (sodium/glucose cotransporter), member 1
• solute carrier family 5 (sodium/glucose transporter), member 1

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Glucose-galactose malabsorption is a rare disorder; only a few hundred cases have been identified worldwide. However, as many as 10 percent of the population may have a somewhat reduced capacity for glucose absorption without associated health problems.