1 WHAT IS NEW OR DIFFERENT

• Addition of recently described subtypes of monogenic diabetes, including causes associated with diabetes in infancy (CNOT1, ONECUT1, YIPF5, EIF2B1, KCNMA1); and genetic causes associated with diabetes later in life (TRMT10A, DNAJC3, KCNK16, DUT).
• The expanding list of genes causing monogenic diabetes further emphasizes comprehensive next-generation sequencing (NGS) as the best approach to allow for early molecular diagnosis that can guide treatment, rather than phenotype-based targeted testing, particularly for neonatal diabetes (NDM).
• Use of increasingly available publicly accessible information about specific variants to allow for the appropriate classification of pathogenicity of gene variants according to guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), bolstered by the establishment of international Monogenic Diabetes Expert Panels for gene curation and variant curation with the elaboration of gene-specific rules (https://clinicalgenome.org/affiliation/50016).
• Further understanding of the neuroendocrine aspects of ATP-sensitive potassium channel (KATP) related NDM (KATP-NDM) is now included.
• Clarification that a small fraction of NDM is likely to be autoimmune type 1 diabetes (T1D) and autoimmune etiology distinct from T1D occurring in Trisomy 21.
• Among young persons with diabetes with a clinical diagnosis of type 2 diabetes (T2D), a low but significant fraction can be found to carry pathogenic MODY mutations; highlighting the importance of considering a monogenic cause even when obesity may be present.
• The rate of diabetes-related complications may be lower in HNF1A diabetes who have been treated with sulfonylureas (SU).
• Liver (with or without pancreas) transplantation can improve the outcomes of individuals with Wolcott-Rallison syndrome.

中文翻译：

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ISPAD 临床实践共识指南 2022：儿童和青少年单基因糖尿病的诊断和管理

1 什么是新的或不同的

• 添加最近描述的单基因糖尿病亚型，包括与婴儿期糖尿病相关的原因（CNOT1、ONECUT1、YIPF5、EIF2B1、KCNMA1）；以及与晚年糖尿病相关的遗传原因（TRMT10A、DNAJC3、KCNK16、DU T）。
• 导致单基因糖尿病的基因列表不断扩大，进一步强调全面的下一代测序 (NGS) 是进行早期分子诊断以指导治疗的最佳方法，而不是基于表型的靶向检测，特别是对于新生儿糖尿病 (NDM)。
• 根据美国医学遗传学和基因组学学会和分子病理学协会 (ACMG/AMP) 的指南，使用越来越多的关于特定变异的可公开获取的信息，以允许对基因变异的致病性进行适当分类，并得到建立用于基因管理和变异管理的国际单基因糖尿病专家小组制定了基因特异性规则 (https://clinicalgenome.org/affiliation/50016)。
• 现在包括对 ATP 敏感钾通道 (KATP) 相关 NDM (KATP-NDM) 的神经内分泌方面的进一步了解。
• 澄清一小部分 NDM 可能是自身免疫性 1 型糖尿病 (T1D) 和与 21 三体综合征中发生的 T1D 不同的自身免疫病因。
• 在临床诊断为 2 型糖尿病 (T2D) 的年轻糖尿病患者中，可以发现一小部分但很重要的部分携带致病性 MODY 突变；强调即使可能存在肥胖，也要考虑单基因原因的重要性。
• 接受过磺脲类药物 (SU) 治疗的 HNF1A 型糖尿病患者的糖尿病相关并发症发生率可能较低。
• 肝脏（有或没有胰腺）移植可以改善 Wolcott-Rallison 综合征患者的预后。