Congenital diarrhoea refers to a heterogeneous group of enteropathies that cause symptoms from the first few days of life, and it may be the only manifestation or one of the symptoms of a systemic disease. In most cases, early treatment is necessary to prevent dehydration, given the potential complications of the latter. The first step in the differential diagnosis is to differentiate between secretory and osmotic diarrhoea: in the former, the diarrhoeal output does not improve with a nil per os trial, whereas in the latter it does.1

We present the case of a male newborn aged 2 days admitted to the neonatal unit with hyperbilirubinaemia. The parents were Pakistani and reported consanguinity. The newborn was a product of a monochorionic-diamniotic twin pregnancy and had been born second at 36 weeks’ gestation with a weight of 2460g. He was receiving artificial formula following the wishes of the mother. On admission to the neonatal unit, the physical examination revealed a 15% weight loss, jaundice extending to Kramer's zone 3 and a dry oral mucosa, with no other abnormal findings. Blood tests revealed hyperbilirubinaemia on account of elevation of indirect bilirubin and dehydration with hypernatraemia and hyperchloraemia (urea, 49mg/dL; creatinine, 1.5mg/dL; sodium, 163mEq/L; chloride, 132mEq/L) and metabolic acidosis (pH, 7.30; bicarbonate, 18.7mM; base excess, 7mM; lactate, 3.9mM). Phototherapy was initiated, along with placement of a peripheral catheter for intravenous fluid replacement, while the patient continued to receive artificial formula. The diarrhoeal output continued to be very high, leading to prescription of nil per os, which achieved resolution of the diarrhoea. The analysis of stool samples revealed an acidic pH and the presence of reducing bodies. In the following days, several attempts were made to reintroduce oral feedings, first with elemental formula and later with a soy-based formula, with diarrhoea recurring in both instances as the feeding volume increased. Eventually, the newborn was given a fructose-based formula with no other carbohydrates, to which he responded favourably. Increases in feeding volume did not create problems, and the boy started producing normal stools and exhibiting adequate weight gain.

In this case, since the patient improved with fasting, the diarrhoea was classified as osmotic, and the presence of reducing bodies in the stool suggested that the congenital diarrhoea could be due to carbohydrate malabsorption. Since the patient did not improve with the soy formula, we suspected glucose–galactose malabsorption,1 as soy formulas do not contain galactose but do contain glucose. In fact, upon switching to a formula in which the sole carbohydrate was fructose, the newborn responded well, which supported our clinical suspicion.

Congenital glucose–galactose malabsorption (cGGM) is a rare autosomal recessive disorder characterised by changes in the SLC5A1 gene that encodes the protein SGLT1, responsible for transporting glucose and galactose from the intestinal lumen into intestinal cells.2 Sequencing of this gene in the patient revealed the homozygous mutation c.875G>A (p.C292Y), previously described as a pathogenic variant, as it impacts the location and function of the protein,3 thus confirming the diagnosis. Microsatellite genotyping confirmed that the twins were dizygotic, which explained the clinical differences between the two.

Congenital glucose–galactose malabsorption is characterised by severe diarrhoea and dehydration from the first day of life, which can quickly result in the death of the infant if glucose, galactose and the disaccharides that contain them are not removed from the diet.4 Approximately 300 cases have been diagnosed worldwide.5 Treatment consists in the elimination of glucose and galactose from the diet, substituting a fructose-based formula, which achieves resolution of diarrhoea. Some authors have proposed that cGGM improves over time as the intestinal flora adapts, and it appears that administration of Lactobacillus acidophilus helps shorten the time that carbohydrates need to be restricted.6 However, there are no prospective studies in the literature establishing how to identify which patients will develop tolerance and which will remain intolerant for life, so we currently recommend that older children and adults consume a diet where fructose is the sole source of carbohydrates until tolerance can be evaluated.