Feigerlová E, Pruhová S, Dittertová L, Lebl J, Pinterová D, Kolostová K, Cerná M, Pedersen O, Hansen T
Department of Paediatrics, 3rd Faculty of Medicine, Charles University, Vinohradska 159, 100 81, Prague 10, Czech Republic.
Eur J Pediatr. 2006 Jul;165(7):446-52. doi: 10.1007/s00431-006-0106-3. Epub 2006 Apr 7.
Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic beta-cell dysfunction.
We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents.
We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1alpha (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4alpha (HNF4A) (those with a positive family history of diabetes).
We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.
无症状个体中随机估计的空腹血糖升高可能是胰腺β细胞功能障碍的首个迹象。
我们旨在明确一组儿童和青少年无症状高血糖的遗传病因。
我们分析了82名非肥胖儿科患者（38名男性）的病因诊断，这些患者年龄在0.2至18.5岁之间（中位数：13.1岁），因随机发现血糖水平高于5.5 mmol/l而前来就诊。除了空腹血糖、胰岛素和C肽的循环水平外，还对这些患者进行了口服葡萄糖耐量试验和静脉葡萄糖耐量试验，并筛查了编码葡萄糖激酶（GCK）、肝细胞核因子-1α（HNF-1α，即TCF1）、Kir6.2（KCNJ11）（年龄<2岁者）和肝细胞核因子-4α（HNF-4α，即HNF4A）（有糖尿病家族史者）的基因突变。
我们鉴定出35名携带导致青少年发病的成年型糖尿病2型（MODY2）的GCK基因突变携带者、2名携带导致青少年发病的成年型糖尿病3型（MODY3）的TCF1基因突变携带者、1名携带导致青少年发病的成年型糖尿病1型（MODY1）的HNF4A基因突变携带者以及1名携带导致永久性新生儿糖尿病的KCNJ11基因突变携带者。其余患者中，11人进展为1型糖尿病（T1DM），9人糖耐量受损或患有病因不明的糖尿病。23名患者的血糖水平异常未得到证实。我们得出结论，82名随机发现空腹血糖升高的儿科患者中有39名（48%）患有单基因缺陷疾病，其中MODY2最为常见。另外11名患者（13%）进展为显性T1DM。对无症状高血糖儿童和青少年进行病因诊断有助于引入早期有效治疗，或在MODY2患者中避免未来进行任何广泛的再次检查。
