Supplementary Material for: A case of hyperinsulinemic hypoglycemia associated with atypical Fanconi renal tubulopathy syndrome caused by an HNF4A variant

This case illustrates the challenges in the diagnosis of a rare disease with an intricate orientation, requiring an in-depth medical history review and a comprehensive series of laboratory tests with genetic confirmation. The patient presented with myoclonic jerks associated with hypoglycaemia and proximal tubulopathy. A fasting functional test was performed to investigate the origin of the hypoglycaemia. The identification of inadequate insulin suppression with hypoketotic hypoglycaemia led to the diagnosis of hyperinsulinaemic hypoglycaemia (HH). In addition, the diagnosis of chronic renal dysfunction associated with atypical Fanconi renal tubulopathy syndrome (FRTS) was indicated on the basis of a decreased estimated glomerular filtration rate (eGFR), nephrocalcinosis, millimetric lithiasis, rickets and complex proximal tubulopathy, among other laboratory findings. The association of atypical FRTS with HH was an indication for molecular genetic testing. The patient was identified as a carrier of the c.187C>T (p.Arg63Trp) variant in the HNF4A gene, which is a heterozygous missense variant classified as pathogenic. This entity is rare, and the published literature reporting HNF4A gene variants associated with atypical FRTS and HH is limited. It is therefore important to report such cases to contribute to the growing body of evidence and help identify pathogenic HNF4A variants and their implications.