UNLABELLED

Congenital glucose-galactose malabsorption (CGGM) is a rare autosomal recessive disorder caused by a biallelic mutation of solute carrier family 5 member 1 (), encoding the sodium-dependent glucose transport-1 (SGLT-1) protein. Patients with CGGM present with neonatal-onset osmotic diarrhea due to impaired intestinal uptake of glucose. Here, we report a case of a 41-year-old female with CGGM who was referred to our clinic for symptoms of hypoglycemia, with the final diagnosis of an insulinoma, which was successfully resected. Whole genome sequencing of tumor DNA revealed chromosomal aberrations, without the presence of driver mutations. Given the unknown long-term sequelae of SGLT-1 loss of function in adulthood, this first case of insulinoma in a CGGM patient potentially uncovers a new phenotype resulting from decades of imbalance in glucose homeostasis. We hypothesize that SGLT-1 might play a role in the plasticity of pancreatic β-cells and suggest mechanisms through which CGGM patients could potentially have a higher risk of developing insulinoma in adulthood.

LEARNING POINTS

This is the first documented case of insulinoma in a patient with CGGM, suggesting a potential new link between glucose absorption disorders and pancreatic neuroendocrine tumors.The loss-of-function mutation in SGLT-1 due to an SLC5A1 gene mutation may impact pancreatic β-cell plasticity, potentially contributing to insulinoma development through altered glucose homeostasis.The patient's long-term high-fat, low-carbohydrate diet may have played a role in β-cell stimulation via increased levels of GLP-1 and GIP, both of which promote β-cell proliferation and survival.