Imerslund-Grasbeck syndrome associated with recurrent aphthous stomatitis and defective neutrophil function

Vitamin B12 deficiency is a well-known cause of recurrent aphthous stomatitis (RAS). However, the mechanism by which this deficiency causes the stomatitis is not well understood. Imerslund-Grasbeck syndrome (IGS) causes vitamin B12 deficiency and proteinuria due to a defect in the vitamin B12 receptor. We sought to determine whether the RAS observed in IGS patients is associated with neutrophil dysfunction. We report 3 infants with vitamin B12 deficiency due to IGS, who presented with borderline or normal hemoglobin concentrations, RAS, and a neutrophil function defect. All 3 patients were homozygous for a splice site mutation affecting exon 4 of the AMN gene. A direct correlation was observed between low serum vitamin B12 levels and defective neutrophil function (low chemotaxis and elevated superoxide production) in the patients. Vitamin B12 therapy led to an immediate resolution of aphthous stomatitis and full correction of neutrophil function. We demonstrated that serum vitamin B12 deficiency is associated with a neutrophil chemotactic defect and RAS in IGS patients. We suggest that the RAS observed in these patients is due to this defect.