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Testing for monogenic diabetes among children and adolescents with antibody‐negative clinically defined Type 1 diabetes
Author(s) -
RubioCabezas O.,
Edghill E. L.,
Argente J.,
Hattersley A. T.
Publication year - 2009
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2009.02812.x
Subject(s) - medicine , hnf1a , autoantibody , type 1 diabetes , diabetes mellitus , type 2 diabetes , diabetic ketoacidosis , ketoacidosis , maturity onset diabetes of the young , endocrinology , antibody , gastroenterology , immunology
Aims Monogenic diabetes is frequently misdiagnosed as Type 1 diabetes. We aimed to screen for undiagnosed monogenic diabetes in a cohort of children who had a clinical diagnosis of Type 1 diabetes but were pancreatic autoantibody‐negative. Methods We studied 252 patients diagnosed clinically with Type 1 diabetes between 6 months and 17 years of age. Pancreatic autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase antibodies (GADA) and/or insulinoma‐associated antigen‐2 antibodies (IA2A)] were absent in 25 cases (9.9%). The most frequent genes involved in monogenic diabetes [ KCNJ11 and INS for neonatal diabetes and HNF1A and HNF4A for maturity‐onset diabetes of the young (MODY)] were directly sequenced. Results Two of the 25 (8%) antibody‐negative patients had de novo heterozygous mutations in INS ; c.94G>A (G32S) and c.265C>T (R89C). The two patients presented with non‐ketotic hyperglycaemia at 8 and 11 months of age. In contrast, the four antibody‐positive patients who presented at a similar age (6–12 months) had a more severe metabolic derangement, manifested as ketosis in all four cases, with ketoacidosis in two. At ages 15 and 5 years, both INS mutation patients were prescribed a replacement dose of insulin with good glycaemic control [glycated haemoglobin (HbA 1c ) 7.0 and 7.2%]. No mutations were found in KCNJ11 , HNF1A or HNF4A . Conclusions The identification of patients with monogenic diabetes from children with clinically defined Type 1 diabetes may be helped by clinical criteria including the absence of pancreatic autoantibodies.