title: Acute metabolic acidosis in a GLUT2-deficient patient with Fanconi-Bickel syndrome: new pathophysiology insights.
abstract: Fanconi-Bickel syndrome is a rare autosomal-recessive disorder caused by mutations in the SLC2A2 gene coding for the glucose transporter protein 2 (GLUT2). Major manifestations include hepatomegaly, glucose intolerance, post-prandial hypoglycaemia and renal disease that usually presents as proximal tubular acidosis associated with proximal tubule dysfunction (renal Fanconi syndrome). We report a patient harbouring a homozygous mutation of SLC2A2 who presented a dramatic exacerbation of metabolic acidosis in the context of a viral infection, owing to both ketosis and major urinary bicarbonate loss. The kidney biopsy revealed nuclear and cytoplasmic accumulation of glycogen in proximal tubule cells, a lack of expression of GLUT2, and major defects of key proteins of the proximal tubule such as megalin, cubilin and the B2 subunit of H(+)-ATPase. These profound alterations of the transport systems most likely contributed to proximal tubule alterations and profound bicarbonate loss.
authors.affiliation: Department of Nephrology and Dialysis, AP-HP, Tenon Hospital, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Mihout
authors.affiliation: Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Department of Pediatric Nephrology, AP-HP, Robert Debré Hospital, Paris, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Bensman
authors.affiliation: Department of Pathology, AP-HP, Tenon Hospital, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.affiliation: Department of Renal Emergency and Kidney Transplantation, AP-HP, Tenon Hospital, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ridel
authors.affiliation: Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Nilufar
authors.initials: N
authors.lastname: Mohebbi
authors.affiliation: Department of Nephrology and Dialysis, AP-HP, Tenon Hospital, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France INSERM, UMR_S 1155, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: Department of Nephrology and Dialysis, AP-HP, Tenon Hospital, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France INSERM, UMR_S 1155, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Plaisier
authors.affiliation: Department of Nephrology and Dialysis, AP-HP, Tenon Hospital, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1155, Paris, France INSERM, UMR_S 1155, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
mesh_terms: D000138:Acidosis / Q000235:genetics / Q000503:physiopathology*; D000208:Acute Disease; D005198:Fanconi Syndrome / Q000235:genetics / Q000503:physiopathology*; D051273:Glucose Transporter Type 2 / Q000172:deficiency / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: D051273:Glucose Transporter Type 2; C495680:SLC2A2 protein, human
keywords: Fanconi–Bickel; SLC12A2; ketosic acidosis; metabolic acidosis; proximal tubular nephropathy