Glucose and galactose absorption disorder

The glucose-galactose malabsorption is a rare genetic disorder that holds significant importance within metabolic disorders. This condition is inherited in an autosomal recessive manner, meaning that the defective gene must be inherited from both parents for the disease to manifest. The failure to absorb glucose and galactose in the intestine can have severe consequences, as the proper utilization of nutrients is essential for the healthy functioning of the body.

The underlying cause of the disease is a mutation in the SLC5A1 gene, which is responsible for the function of the sodium/glucose cotransporter 1 (SGLT1). Under normal circumstances, this transporter allows glucose and galactose to be transported from the small intestine into the intestinal cells. However, when the gene is mutated, the efficiency of the transporter is reduced or lost, leading to the accumulation of nutrients in the intestine and water retention. As a consequence, osmotic diarrhea may develop, which can cause further complications.

Glucose-galactose malabsorption is a condition that requires diagnosis and treatment, demanding appropriate attention and expertise for early detection.

The Symptoms of Glucose-Galactose Malabsorption

The symptoms of glucose-galactose malabsorption typically present in infancy when the infant is first fed breast milk or lactose-containing formula. The most characteristic symptoms include severe, watery diarrhea, which causes significant fluid loss, leading to dehydration and electrolyte imbalances. These imbalances can manifest as low sodium and potassium levels, as well as metabolic acidosis, which in severe cases can lead to life-threatening conditions.

The diarrhea symptoms cease once the patient is placed on a diet free of glucose and galactose. It is worth mentioning that in some cases, the diagnosis may be delayed, or the initial signs may only be mildly present. This may be due to genetic heterogeneity, as mutations in the SLC5A1 gene can cause varying degrees of functional loss. In cases of partial functional loss, the SGLT1 transporter may remain somewhat functional, allowing symptoms to appear later or in a milder form.

It is rare for the problem to become apparent not in infancy but later, such as in toddlerhood or childhood. This primarily occurs when the amount of glucose and galactose in the child’s diet gradually increases. At this point, symptoms may present as chronic diarrhea, developmental delays, and recurrent dehydration.

The Diagnostic Process

The diagnosis of glucose-galactose malabsorption requires particular attention, as the rarity of the disease often leads to confusion with other conditions. The most important thing is to consider the possibility of glucose-galactose malabsorption when characteristic symptoms appear, even if the disease is rare. Special attention should be given to refractory watery diarrhea that only improves with parenteral nutrition.

Laboratory tests are necessary to establish the diagnosis. The first step is to examine the stool osmolality and the presence of reducing sugars. Following the administration of glucose or galactose, a positive reaction in the stool is expected. Although this test cannot be performed in infancy, it can be applied in later-presenting forms.

Molecular genetic testing must demonstrate a mutation in the SLC5A1 gene, which confirms the diagnosis. It is essential to differentiate from other congenital malabsorption syndromes, such as congenital lactose intolerance or congenital chloride diarrhea, during the differential diagnosis.

Complications and Treatment Options

Glucose-galactose malabsorption can lead to several complications, which can be categorized into two main groups: acute and chronic problems. The most commonly occurring acute complications in neonates and infants include severe dehydration, which can cause hypovolemic shock. Additionally, electrolyte imbalances, such as hyponatremia and metabolic acidosis, may also develop.

In cases of chronic malabsorption, long-term consequences may include developmental delays, malnutrition, vitamin and mineral deficiencies, and a weakened immune system, making children more susceptible to infections. Neurocognitive development may also be delayed as a result of chronic hypoglycemia, malnutrition, and dehydration.

Treatment of the disease requires a lifelong diet that is free from glucose and galactose. Complete withdrawal of breast milk and conventional formulas is necessary, as dietary violations can quickly lead to severe symptoms. Fructose can be used as an alternative carbohydrate source, as it is absorbed via the GLUT5 transporter, independent of the disease’s effects. Fructose-based specialized infant formulas are also available, which can assist in nutrition.

The prognosis is favorable if the disease is recognized early and the appropriate diet is adhered to. Children have the potential for normal physical and mental development; however, in cases of late diagnosis, the risk of developmental and well-being issues increases due to chronic energy and fluid deficiencies. The introduction of a glucose- and galactose-free diet can significantly improve the prognosis and help prevent complications.