新生儿糖尿病（neonatal diabetes mellitus,NDM）是一种罕见的单基因病,临床表现隐匿,临床表型与基因型异质性大,容易延误诊断。近年来,随着基因检测技术的发展,越来越多的致病基因逐渐被认识,目前已知的有30多种基因变异可引起NDM,不同亚型的NDM在临床表现、治疗和转归等方面有所不同。染色体6q24印记区域的基因变异或甲基化异常是暂时性新生儿糖尿病（transient neonatal diabetes mellitus,TNDM）最常见的原因,ATP敏感性钾通道（K_ATP）基因（KCNJ11、ABCC8）变异是持续性新生儿糖尿病（persistent neonatal diabetes mellitus,PNDM）的最常见原因。NDM常需胰岛素替代治疗,而大约90%的KCNJ11或ABCC8变异的NDM患儿口服磺脲类药物治疗可维持稳定血糖水平,早期治疗还可逆转部分KCNJ11变异导致的神经发育迟缓,同时可增加从胰岛素转换至磺脲类药物治疗的成功率。早期明确遗传学诊断和分型有助于实现精准个体化治疗,判断预后。本文就NDM的基因型-临床表型及治疗、管理等进行归纳、总结,为儿科医生在临床诊疗中早期发现、早期诊断以及精准治疗提供参考。

Neonatal diabetes mellitus (NDM) is a rare monogenic disease with extensive heterogeneity in clinical phenotypes and genotypes on hidden clinical manifestations, which can easily delay diagnosis. In recent years, with the development of gene detection technology, more pathogenic genes have been gradually recognized. At present, more than 30 gene mutations are known as varied subtypes of NDM for the differences on clinical manifestations and outcomes. Genetic variation or abnormal methylation in chromosome 6q24 imprinting region is the commonest cause of transient neonatal diabetes mellitus (TNDM), and KATP gene mutations (KCNJ11, ABCC8) are the commonest cause of persistent neonatal diabetes mellitus (PNDM). About 90% of NDM children with KCNJ11 or ABCC8 mutations received oral sulfonylureas to maintain stable blood glucose levels. Early treatment can reverse part of the neurodevelopmental delay caused by KCNJ11 mutations, and improve the success rate of insulin conversion to sulfonylureas. Early accurate genetic diagnosis and typing are helpful for precise individualized treatment and prognosis determination. In this paper, genotype-phenotype, treatment and management of NDM were summarized, providing reference for pediatricians in early detection and diagnosis, precise treatment in clinical practice.