Congenital glucose-galactose malabsorption (CGGM) is a rare autosomal recessive disorder produced by an alteration in the sodium-glucose cotransporter 1 (SGLT1), located on the brush border of the small bowel. It is responsible for the absorption of glucose and galactose, transporting them from the intestinal lumen into the enterocyte, driven by the transmembrane sodium electrochemical gradient (Fig. 1). Congenital SGLT1 deficiency is secondary to mutations of the SLC5A1 gene located on chromosome 22q13.1.1,2

Figure 1.

a) SGLT 1 transporter: It carries out the active transport of glucose and galactose in the enterocyte against a concentration gradient, from the intestinal lumen into the enterocyte. The energy required for making this transport possible is acquired from sodium cotransportation in the same direction. b) absence of the SGLT 1 transporter: When glucose and galactose are not absorbed, these sugars remain in the intestinal lumen and draw water out due to the osmotic effect, leading to osmotic diarrhea and severe dehydration.3 The net result is a greater loss of water than sodium, and in turn, sodium becomes concentrated in the plasma, resulting in hypernatremia.

At present, approximately 300 cases have been reported worldwide.3 A high level of suspicion is required for its diagnosis and lack of early detection may be potentially fatal.

A 44-day-old female infant was the product of a second pregnancy, whose mother had no prenatal control and a history of consanguinity. The infant was delivered at 37 weeks by cesarean section, weighing 2865 g and measuring 49 cm in length. At 10 minutes from birth, she presented with respiratory difficulty and then abdominal distention. A biliary drainage catheter was placed. Early neonatal sepsis and necrotizing enterocolitis were suspected, and antibiotics and fasting for 5 days were indicated. Tests for infections were negative. Maternal breastfeeding was begun and the neonate presented with liquid stools, with up to 10 episodes daily. This conditioned severe dehydration, oral feeding intolerance, and severe weight loss (13.4%). Cow’s milk protein allergy was suspected, and the mother was placed on a restricted diet. Elemental and hydrolyzed formula was given to the infant, but vomiting and high-output diarrhea persisted. The patient presented with hyperchloremic metabolic acidosis and hypernatremia, unresponsive to water deficit replacement therapy.

Physical examination on admission: sunken fontanelle, distended abdomen, and increased peristalsis. Anthropometry: weight 2800 g (weight-for-length: –1.35 SD), length 49 cm (length-for-age: –3.41 SD). A tendency toward polyuria was recorded. Laboratory work-up: high anion gap metabolic acidosis, hypernatremia, hyperchloremia, and azotemia (Table 1). Plain abdominal x-ray: air-fluid levels; abdominal ultrasound: moderate intestinal segment distension. CGGM was suspected. A bladder catheter was placed, showing that the losses were predominantly gastrointestinal. Fasting with total parenteral nutrition was indicated, observing improved fecal output. A homemade formula based on fructose, protein, and olive oil, associated with multivitamins and trace elements, was started (Table 2). The infant tolerated enteral nutrition in progressive volumes, resolving her gastrointestinal symptoms.

Control laboratory work-up: improvement in the metabolic acidosis, anion gap, hypernatremia, azotemia, and glomerular filtration rate. Tubulopathy was ruled out. Genetic study confirmed a homozygous mutation c.1673G > A (p.Arg558His) in the SLC5A1 gene.

After 2 weeks of nutritional management the patient recovered her weight (3450 g) and diarrhea improved. She was discharged with glucose and galactose restriction.

The patient is currently 16 months old and tolerates the established homemade formula, associated with a complementary diet restricted in glucose and galactose-rich foods. Her bowel movements are consistent, twice a day, and she is gaining weight and growing. Laboratory results show normal electrolytes, a negative Sudan III test, stable kidney function, and normal hemogram.

High-output osmotic diarrhea in CGGM is due to carbohydrate malabsorption (glucose and galactose), which when not absorbed in the small bowel, are fermented by colonic bacteria, producing short-chain fatty acids that cause watery and acidic stools (fecal pH < 5.3) that can be confused with urine,4 as occurred with our patient. This type of diarrhea leads to hypernatremic dehydration, metabolic acidosis, weight loss, abdominal distension, cramping, vomiting, polyuria, nephrolithiasis, nephrocalcinosis, and kidney function deterioration due to chronic dehydration.5 The mean time to diagnosis is approximately 8 weeks but can be delayed for up to 4.5 months.6 Diagnosis starts with clinical suspicion; elimination of glucose and galactose from the diet resolves the diarrhea almost immediately, which is why these patients respond favorably to fasting.7Fig. 2 describes the diagnostic criteria. Diagnosis is confirmed through the study of SLC5A1 gene mutations.8 The homozygous mutation p.Arg558His/c.1673G>A in the SLC5A1 gene has been described as causing CGGM.3 The clinical diagnosis in our patient was made at her seventh week of life, based on the association of chronic diarrhea and persistent hypernatremia. Because the expected electrolyte alteration in diarrhea is hyponatremia, the presence of persistent hypernatremia in high-output diarrhea in a young patient is suggestive of CGGM. Thanks to timely suspicion, empiric nutritional management could be started that rapidly controlled the patient’s symptoms, while genetic testing was being conducted.

Figure 2.

CGGM diagnostic criteria.

Treatment is nutritional, based on formulas with fructose, because that monosaccharide has a transporter different from SGLT-1, called GLUT5. There are 2 formulas on the market: RCF (Abbott Nutrition) and Galactomin 19, (Nutricia),9 but they are not available in Colombia. Therefore, our patient received a homemade formula, based on fructose (Table 2), which resolved her symptoms. Nutritional management offers good prognosis. Small quantities of glucose may be tolerated in the short and medium terms, and even larger quantities in the long term, with no diarrhea.10

In conclusion, the prompt recognition of CGGM enables its adequate management, reducing the morbidity and mortality of the disease. To the best of our knowledge, ours is the first case reported in Colombia, with genetic confirmation of mutation c.1673G>A (p. Arg558His) in the SLC5A1 gene. This finding is a point of departure for future studies evaluating the prevalence of SLC5A1 mutations in Latin America and its implications for genetic counseling.