Testing for monogenic diabetes among children and adolescents with antibody-negative clinically defined Type 1 diabetes
Testing for monogenic diabetes among children and adolescents with antibody-negative clinically defined Type 1 diabetes
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DOI：
10.1111/j.1464-5491.2009.02812.x
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发表时间：
2009-10-01
影响因子：
3.5
通讯作者：
Hattersley, A. T.
中科院分区：
文献类型：
--
作者：
Rubio-Cabezas, O.;Edghill, E. L.;Hattersley, A. T.
目的单基因糖尿病常被误诊为1型糖尿病。我们的目标是在一组临床诊断为1型糖尿病但胰腺自身抗体阴性的儿童中筛查未诊断的单基因糖尿病。方法我们研究了252名6个月至17岁的临床诊断为1型糖尿病的患者。胰腺自身抗体[胰岛细胞自身抗体(ICA)、谷氨酸脱羧酶抗体(GADA)和/或胰岛素瘤相关抗原-2抗体(IA2A)]缺失者25例(9.9%)。结果在25例抗体阴性的糖尿病患者中，2例(8%)存在INS、C.94G>；A(G32S)和C.265C>；T(R89C)的新生杂合突变。这两名患者分别在8个月和11个月大时出现非酮症高血糖。相比之下，年龄相近(6-12个月)的4名抗体阳性患者的代谢紊乱更严重，所有4例患者都表现为酮症，其中2例伴有酮症酸中毒。在15岁和5岁时，两名INS突变患者都接受了血糖控制良好的胰岛素替代剂量[糖化血红蛋白(HbA(1c))7.0和7.2%]。未发现KCNJ11、HNF1A或HNF4A基因突变。结论临床诊断标准包括无胰腺自身抗体有助于从临床确诊的1型糖尿病儿童中鉴别出单基因糖尿病患者。
AimsMonogenic 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.MethodsWe 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.ResultsTwo 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.ConclusionsThe 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.