title: Imerslund-Grasbeck syndrome associated with recurrent aphthous stomatitis and defective neutrophil function.
abstract: Vitamin B(12) 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 B(12) deficiency and proteinuria due to a defect in the vitamin B(12) receptor. We sought to determine whether the RAS observed in IGS patients is associated with neutrophil dysfunction. We report 3 infants with vitamin B(12) 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 B(12) therapy led to an immediate resolution of aphthous stomatitis and full correction of neutrophil function. We demonstrated that serum vitamin B(12) 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.
authors.affiliation: Pediatric Immunology Clinic, Soroka Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. broides@bgu.ac.il
authors.forename: Arnon
authors.initials: A
authors.lastname: Broides
authors.forename: Baruch
authors.initials: B
authors.lastname: Yerushalmi
authors.forename: Rachel
authors.initials: R
authors.lastname: Levy
authors.forename: Nurit
authors.initials: N
authors.lastname: Hadad
authors.forename: Norma
authors.initials: N
authors.lastname: Kaplun
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Tanner
authors.forename: Allbert de la
authors.initials: Ade L
authors.lastname: Chapelle
authors.forename: Jacov
authors.initials: J
authors.lastname: Levy
mesh_terms: D000749:Anemia, Megaloblastic / Q000150:complications*; D002633:Chemotaxis; D003241:Consanguinity; D004200:Diseases in Twins / Q000175:diagnosis; D005260:Female; D006801:Humans; D007223:Infant; D007960:Leukocyte Disorders / Q000150:complications*; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D009504:Neutrophils / Q000502:physiology*; D011506:Proteins / Q000235:genetics; D013281:Stomatitis, Aphthous / Q000150:complications* / Q000188:drug therapy; D013481:Superoxides / Q000378:metabolism; D013577:Syndrome; D014805:Vitamin B 12 / Q000627:therapeutic use; D014804:Vitamin B Deficiency / Q000150:complications* / Q000235:genetics
chemical_list: C484714:AMN protein, human; D008565:Membrane Proteins; D011506:Proteins; D013481:Superoxides; D014805:Vitamin B 12