ClinVar

In a patient with fructose intolerance (HFI; 229600), Esposito et al. (2010) identified a heterozygous 136A-T transversion in exon 3 of the ALDOB gene, resulting in an arg46-to-trp (R46W) substitution in a conserved residue. The mutation was not found in 300 control alleles. A second mutation or deletion in the ALDOB gene was excluded, indicating that the patient was heterozygous for the mutation. The patient had mild hypoglycemia and ketosis after ingestion of fructose and a marked aversion to sweets and fruit. In vitro functional expression assays showed that the R46W variant had 14-fold lower catalytic efficiency for fructose-1-phosphate compared to wildtype, with no apparent change for fructose bisphosphate. Structural analysis showed that the arg46 residue is far from the tetramer interface and has structural flexibility, but loss of the positively charged arg46 residue may alter binding of fructose-1-phosphate. The report emphasized that heterozygous ALDOB mutations may result in symptoms in some patients.