Identification of an unusual variant of Fanconi-Bickel syndrome presenting as proximal tubulopathy and short stature

Fanconi-Bickel syndrome (FBS) is caused by biallelic pathogenic variants in the SLC2A2 gene, which encodes the glucose transporter protein 2 (GLUT2), leading to a rare disorder that affects glucose homeostasis. The exact mechanisms by which FBS leads to dysglycaemia are not clearly understood. The clinical manifestations are those related to dysglycaemia, proximal tubulopathy (glycosuria, galactosuria, aminoaciduria, proteinuria, phosphaturia), hepatomegaly, galactose intolerance, rickets and short stature.We report a teenage girl with persistent glycosuria and short stature. Laboratory findings revealed glycosuria, proteinuria, aminoaciduria, hypercalciuria and hypouricaemia indicating a proximal tubulopathy. Whole exome sequencing identified two variants, c.218C>G p.(Ser73*) and c.371+5G>A, likely in trans in the SLC2A2 gene, establishing the diagnosis of FBS. She was asymptomatic, and the treatment consisted of vitamin D supplementation and dietary changes.FBS may have a wide range of clinical manifestations and severity. Abnormal laboratory results indicating glucose metabolism issues are crucial diagnostic clues for mild forms of FBS. Indeed, the diagnosis of mild forms of FBS is challenging due to the lack of specific clinical and analytical features.