title: HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months.
abstract: Children with permanent diabetes are usually assumed to have type 1 diabetes. It has recently been shown that there are genetic subgroups of diabetes that are often diagnosed during the neonatal period but may present later. A recent Italian study proposed that type 1 diabetes is rare before 6 months of age. We aimed to examine genetic susceptibility to type 1 diabetes in patients diagnosed with diabetes before the age of 2 years. We analyzed HLA class II genotypes, markers of autoimmune diabetes, in 187 children with permanent diabetes diagnosed at <2 years of age. Of the 79 subjects diagnosed at <6 months of age, 41% (95% CI 0.30-0.51) had type 1 diabetes-associated high-risk genotypes, a proportion similar to that in healthy population control subjects (44%, P=0.56). This group included 32 patients with mutations in the KCNJ11 gene, which encodes Kir6.2 (44% high-risk HLA class II genotypes), and 47 in whom the etiology of diabetes was unknown (38% high-risk HLA class II genotypes). Of 108 patients diagnosed between 6 and 24 months of age, 93% (0.86-0.99) had high-risk HLA class II genotypes compared with 44% of the population control subjects (P<0.0001). We conclude that infants diagnosed with diabetes before 6 months of age are unlikely to have autoimmune type 1 diabetes and are most likely to have a monogenic etiology.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Edghill
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Dix
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Bingley
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillespie
mesh_terms: D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D000099161:Kcnj11 Channel
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel