Henderson Mélanie, Levy Emile, Delvin Edgard, Losekoot Monique, Lambert Marie
Department of Pediatrics, Ste-Justine Hospital and Université de Montréal, Montreal, QC, Canada.
Mol Genet Metab. 2007 Jan;90(1):87-92. doi: 10.1016/j.ymgme.2006.09.006. Epub 2006 Oct 31.
Our objectives were to describe the clinical phenotype of maturity-onset diabetes of the young (MODY) type 2 in a group of French Canadians and estimate its prevalence in this population. Index cases were identified by an abnormal fasting blood glucose (FBG) upon metabolic evaluation for dyslipidemia. Mutational analyses confirmed that all probands and affected family members were positive for the same glucokinase mutation, p.Val226Met. The prevalence of this mutation was estimated from a representative sample of French Canadians. Eleven individuals in 5 different families were diagnosed with MODY 2. Four of the five families originated from the same region in Quebec. In affected children (n = 6), the median age at diagnosis was 7.6 years (range = 2.9-9.4). All were asymptomatic. The range of FBG was 4.4-7.0 mmol/L; 5 out of the 6 pediatric patients had normal FBG values during the course of follow-up. One child presented with consistently normal FBG. Four of the adults who screened positive for MODY 2 had been previously misdiagnosed with type 2 DM, and one female had a history of gestational DM. The estimated prevalence of heterozygotes for the p.Val226Met mutation in French Canadians was 0.057% (95%CI 0.01-0.32%). In conclusion, this report presents the first confirmed case of MODY 2 with persistently normal FBG. In children and adolescents, a normal FBG does not allow for the exclusion of a MODY 2 diagnosis. Our results are consistent with a founder effect for the p.Val226Met glucokinase gene mutation in Quebec, Canada.
我们的目标是描述一组法裔加拿大人中青少年发病的成年型糖尿病（MODY）2型的临床表型，并估计该人群中的患病率。通过对血脂异常进行代谢评估时空腹血糖（FBG）异常来确定索引病例。突变分析证实，所有先证者和受影响的家庭成员均携带相同的葡萄糖激酶突变p.Val226Met。该突变的患病率是根据法裔加拿大人的代表性样本估算得出的。5个不同家庭中的11人被诊断为MODY 2型。这5个家庭中有4个来自魁北克的同一地区。在受影响的儿童（n = 6）中，诊断时的中位年龄为7.6岁（范围 = 2.9 - 9.4岁）。所有儿童均无症状。FBG范围为4.4 - 7.0 mmol/L；6名儿科患者中有5名在随访期间FBG值正常。一名儿童的FBG始终正常。4名筛查出MODY 2型阳性的成年人之前被误诊为2型糖尿病，一名女性有妊娠期糖尿病史。法裔加拿大人中p.Val226Met突变杂合子的估计患病率为0.057%（95%CI 0.01 - 0.32%）。总之，本报告呈现了首例确诊的FBG持续正常的MODY 2型病例。在儿童和青少年中，FBG正常并不能排除MODY 2型的诊断。我们的结果与加拿大魁北克p.Val226Met葡萄糖激酶基因突变的奠基者效应一致。
