Pande Arunkumar R, Chaubey Santosh, Kumar Dinesh, Chandra Kumar P, Geetha Thenral, Sharma Akshita
Department of Endocrinology, Lucknow Endocrine Diabetes and Thyroid Clinic, Uttar Pradesh, India.
Department of Endocrinology, Cairns and Hinterland Hospital and Health Service, 165 The Esplanade Cairns North QLD, Queensland, Australia.
Indian J Endocrinol Metab. 2024 Sep-Oct;28(5):480-487. doi: 10.4103/ijem.ijem_361_23. Epub 2024 Nov 8.
Maturity-onset diabetes of the young (MODY) is a rare group of disorders characterised by impaired functions or development of pancreatic islets and monogenic diabetes at a young age. Diagnosing MODY can be rewarding for both clinicians and patients as it can change the management from generic to targeted therapy.
This study reports the retrospective analysis of data collected from four clinics between March 2016 and February 2023 from Lucknow, a city in northern India. Fifty-three individuals are suspected to be affected by MODY based on ISPAD guidelines. Following a detailed clinical evaluation, they were referred for genetic diagnostic testing.
The cohort consists of 19 females and 34 males with a mean age of diagnosis of 25.3 years and a body mass index of 22.3 Kg/m. Genetic testing detected variants in 13/53 (~24.5%) individuals. Five cases had significant pathogenic/likely pathogenic variants, gene in two [(p.Phe268LeufsTer74) (p.Arg200Gln)], one each in (Arg311His), (p.Ala228GlyfsTer33), and a case with suggestive digenic variants in gene (p.Arg200Gln) and [(p.Leu13Met)]. Variants of uncertain significance (VUSs) with inconclusive evidence of pathogenicity were reported in eight patients, and five were considered to be clinically significant as they are lean young onset, sulfonylurea-responsive, and presented with diabetes without acanthosis nigricans and with high pretest probability. These individuals harboured variants in (p.Thr425_Thr429delinsPro), (p.Ser19Phe), (p.Val681ArgfsTer6), (p.Ile872Met), and (p.Arg221Cys) genes.
We found a diagnostic yield of around 10% of pathogenic or likely pathogenic variants in individuals who were suspected to have MODY. As it is a field that is still evolving, we might consider starting with oral agents under close supervision in those individuals who have VUS; there are some proportions of individuals who might not have classical sulfonylurea-responsive genetic variants, but they might respond to it.
青年发病的成年型糖尿病（MODY）是一组罕见的疾病，其特征是胰岛功能受损或发育异常以及年轻时的单基因糖尿病。诊断MODY对临床医生和患者都有益，因为它可以将治疗从通用治疗转变为靶向治疗。
本研究报告了对2016年3月至2023年2月期间从印度北部城市勒克瑙的四家诊所收集的数据进行的回顾性分析。根据国际儿童和青少年糖尿病学会（ISPAD）指南，53人被怀疑患有MODY。经过详细的临床评估后，他们被转诊进行基因诊断测试。
该队列包括19名女性和34名男性，平均诊断年龄为25.3岁，体重指数为22.3kg/m²。基因检测在13/53（约24.5%）的个体中检测到变异。5例有显著的致病/可能致病变异，其中2例在 基因中[（p.Phe268LeufsTer74）（p.Arg200Gln）]， 基因中各有1例（Arg311His）、（p.Ala228GlyfsTer33），还有1例在 基因（p.Arg200Gln）和 基因[（p.Leu13Met）]中有提示性双基因变异。8例患者报告了致病性证据不确定的意义未明变异（VUS），5例被认为具有临床意义，因为他们是消瘦的年轻起病、对磺脲类药物敏感，且患有无黑棘皮病的糖尿病且预检概率高。这些个体在 基因（p.Thr425_Thr429delinsPro）、 基因（p.Ser19Phe）、 基因（p.Val681ArgfsTer6）、 基因（p.Ile872Met）和 基因（p.Arg221Cys）中存在变异。
我们发现，在疑似患有MODY的个体中，致病或可能致病变异的诊断率约为10%。由于这是一个仍在发展的领域，对于那些有意义未明变异的个体，我们可能会考虑在密切监测下开始使用口服药物；有一部分个体可能没有经典的对磺脲类药物敏感的基因变异，但他们可能对此有反应。
