Clinical Research Unit, Khoo Teck Puat Hospital (KTPH), Singapore.
Department of Endocrinology, Tan Tock Seng Hospital (TTSH), Singapore.
Diabetes Res Clin Pract. 2020 Oct;168:108390. doi: 10.1016/j.diabres.2020.108390. Epub 2020 Aug 25.
Monogenic diabetes (also known as maturity-onset diabetes of the young or MODY) affects a subset of individuals with young-onset diabetes. We report our diagnostic work-up experience for such individuals.
Serving as a regional secondary-care diabetes centre in a multi-ethnic population, we receive referrals to evaluate MODY from endocrinologists in both public and private practice. Key criteria for consideration of genetic-testing are onset age ≤ 35, negative GAD antibody, no history of diabetic ketoacidosis, strong family history of diabetes and BMI < 32.5 kg/m. A monogenic diabetes registry was set up since 2017 to study their disease trajectories.
We identified 30 out of 175 (17.1%) individuals with likely pathogenic/pathogenic variants. Importantly, 29 out of 30 (96.7%) occurred in clinically actionable genes. A continuous scale combining BMI, hs-CRP and HDL provided 80% (P < 0.001) diagnostic accuracy for MODY in our cohort, achieving a negative predictive value of 0.93 and sensitivity at 0.76. Subtyping MODY prior to genetic testing (if desired) will require specialist domain knowledge and additional biomarkers due to its genetic heterogeneity.
Through systematic and structured evaluation, the prevalence of MODY is non-trivial (17.1%) in a referral centre. Diagnostic algorithm combining clinical criteria and readily available biomarkers can support clinical decision for MODY genetic testing.
单基因糖尿病（也称为青年发病的成年型糖尿病或 MODY）影响了一部分起病年龄较轻的糖尿病患者。我们报告了对这些患者的诊断工作经验。
作为一个多民族人群中的区域二级保健糖尿病中心，我们从公共和私人实践的内分泌医生那里收到了评估 MODY 的转诊。考虑进行基因检测的关键标准是发病年龄≤35 岁、GAD 抗体阴性、无糖尿病酮症酸中毒史、强烈的糖尿病家族史和 BMI<32.5kg/m²。自 2017 年以来，我们建立了一个单基因糖尿病登记处，以研究他们的疾病轨迹。
我们在 175 名患者中确定了 30 名（17.1%）可能存在致病性/致病性变异的患者。重要的是，30 名中的 29 名（96.7%）发生在具有临床可操作性的基因中。结合 BMI、hs-CRP 和 HDL 的连续评分在我们的队列中为 MODY 提供了 80%（P<0.001）的诊断准确性，实现了 0.93 的阴性预测值和 0.76 的敏感性。在进行基因检测之前（如果需要）对 MODY 进行亚型分类将需要专门的领域知识和额外的生物标志物，因为其遗传异质性。
通过系统和结构化的评估，在转诊中心 MODY 的患病率相当高（17.1%）。结合临床标准和现成的生物标志物的诊断算法可以为 MODY 基因检测的临床决策提供支持。
