Fig. 1: FBP1 mutations identified in an adult patient with severe hypoglycemic acidosis and its clinico-endocrinological profiles.

Panels a and b demonstrate the results of the oral fructose tolerance test. Oral fructose loading resulted in hypoglycemia accompanied by increased lactate levels. In addition, the 3-hydroxybutyrate levels mildly increased, whereas the free fatty acid (FFA) levels exhibited a robust increase. The patient and a healthy volunteer are shown in red and black, respectively. Panels c–e show the results of the genetic analyses of the FBP1 gene. c Whole-exome sequencing results of the patient and her family. IGV browser visualization of the whole-exome sequencing results revealed a novel compound heterozygous missense mutation in the FBP1 gene: c.491G > A p.G164D and c.581T > C p.F194S. The patient inherited the G164D and F194S mutations from her father and mother, respectively. d Compound heterozygous missense mutations in the FBP1 gene, G164D and F194S, were identified in the patient and validated using Sanger sequence analysis. e Pedigree and genotypes of the family. Solid symbols indicate the G164D allele, and half-solid symbols indicate the F194S allele. Squares denote males, and circles denote females. The arrow indicates the patient. f The FBPase enzyme activity was markedly decreased for the G164D, F194S, and cotransfected constructs compared to that for the WT construct. The data are shown as the mean ± SD. *P < 0.05; **P < 0.01 versus WT (one-way ANOVA test followed by Dunnett’s multiple comparison test). Mock: n = 4, WT: n = 9, G164D: n = 5, F164S: n = 5, G164D + F194S: n = 3. g Structure of the FBP1 dimer based on the protein data bank (DOI: 10.2210/pdb1FBP/pdb) is shown. Cyan sphere: substrate binding site; magenta sphere: metal binding site; blue sphere: AMP binding site. G164D and F194S are shown as a smudge and in lemon color, respectively.