Glucose-galactose malabsorption (GGM) is a rare inherited disease that occurs in an autosomal recessive pattern with only a few populations in the world having been identified (Wright, Turk & Martin, 2002). However, about 10 percent of the population is believed to suffer from mild glucose-galactose malabsorption without harsh related health conditions. The disorder was established through clinical studies by two European groups as the failure of the cells lining up the intestinal tract to absorb and transport simple sugars, or monosaccharides.
GGM is also referred to as carbohydrate intolerance of glucose-galactose or complex carbohydrate intolerance or monosaccharide malabsorption. Glucose and galactose are the two simple sugars transported in the intestinal tract and the disaccharides are sugars such as sucrose and lactose which are made from the combination of two simple sugars. During digestion, disaccharides are broken down into simple sugars. Sucrose is broken down into glucose and fructose while lactose is broken down into glucose and galactose by the enzymes sucrase and lactase respectively. As a result, the two disaccharides cannot be digested by those individuals suffering from the GGM.
The two simple sugars, glucose and galactose have similar chemical structures and the same transport enzymes which enable them to be absorbed in the intestine. In general, GGM affects newborns whose main meal is breast milk which is made up of lactose sugar. Infants with this kind of disorder are characterized by severe diarrhea and dehydration in their body tissues. Other symptoms include a high level of acid in the blood, a condition referred to as acidosis, and a decrease in weight when fed particularly, with breast milk or commercial infant formulas containing glucose and galactose. GGM is a life-threatening condition and in case glucose and galactose intake are not removed from the diet of the patient, it may lead to death. In most cases, diarrhea may cease after 1 hour if glucose, galactose, and lactose are withdrawn from the patient diet.
On the other hand, promptly introduction of these sugars into the patient’s diet returns the GGM condition. Some affected children may also develop kidney stones or severe calcium deposits within their kidneys. Children with GGM can tolerate glucose and galactose in their diet as they grow older (Wright, Turk & Martin, 2002). GGM is caused by the mutations in the SLC5A1 gene which is responsible for producing a sodium/glucose cotransporter protein referred to as SGLT1. The affected individuals have both mutated copies of the gene received from chromosome 22. Half of the populations suffering from GGM are as a result of familial intermarriage where both the parent carries a copy of a mutated gene (Schneider, Kinter & Stirling, 1996).
The sodium/glucose cotransporter protein (SGLT1) transports glucose and galactose across the cell membrane in the intestine and helps in the functioning of epithelial cells which line the walls of the intestinal tract. The epithelial cells are composed of finger-like projections called microvilli which absorb nutrients from food as they pass through the intestine. The microvilli occur in different groups collectively referred to as brush borders.
The active transport of sodium and glucose or galactose by SGLT1 protein maintains the intracellular balance of sodium concentration gradient. The mechanism involves an uptake of two sodium ions followed by absorption of one glucose or galactose into the extra-cellular fluid. The absorbed glucose or galactose then diffuses into the blood capillaries (Schneider, Kinter & Stirling, 1996). The SGLT1 actively transports glucose, galactose, sodium, and water across the brush borders membrane in the absorption process. Failure of the SGLT1 leads to the accumulation of glucose and galactose in the intestine preventing further absorption of these two nutrients. Consequently, water is drawn from the body by the accumulated glucose and galactose in the intestinal tract resulting in harsh dehydration and severe diarrhea.
Careful research studies involving the invitro duodenal biopsies have consistently shown that GGM is caused by the failure of active transport of both glucose and galactose in the body. In this study, an auto-radiographic technique was used to demonstrate that epithelial cells from the patients with GGM were unable to accumulate galactose. In addition, a dramatic reduction in the binding of phlorizin to the brush border membrane of the GGM patient was also noted (Schneider, Kinter & Stirling, 1996).
Phlorizin is the traditional inhibitor of the active transport of sugars in the intestinal tract. Other studies have been carried out to establish whether or not mutations in the sodium-glucose cotransporter gene are responsible for GGM disorder. In this study, the human cDNA (hSGLT1) was isolated, the gene mapped and its chromosomal location identified. The patients suffering from GGM were then screened for mutations in SGLT1 using the Xenopus laevis oocygte expression system to determine whether these caused defects in sugar transport. More than half of the patients identified showed that a mutation was responsible for GGM. This led to the conclusion that mutations in the SGLT1 gene are the main cause of GGM and the sugar transport is impaired mainly because the mutant proteins are either abridged or are not targeted to the cell membrane (Wright, Turk & Martin, 2002).
Even though there is no cure that exists for GGM, the patient may manage the condition by complete removal of lactose, sucrose and glucose in the diets. Individuals suffering from this disorder should take fructose-based solid diet and their supplements until they can tolerate glucose as they age.
References
Wright, M., Turk, E., & Martin, G. (2002). Molecular Basis for Glucose-Galactose Malabsorption. Cell Biochemistry and Biophysics Review. 36, (2), 115 – 121.
Schneider, J., Kinter, B., & Stirling, E. (1996). Glucose-Galactose malabsorption: report of a case with auto-radiographic studies of mucosal biopsy. The New England. Journal of Medicine. 274, 305-312.