Department of Pediatrics, University of Ioannina, 45110 Ioannina, Greece.
Department of Endocrinology & Diabetes Center, University of Ioannina, 45110 Ioannina, Greece.
Int J Mol Sci. 2024 Sep 29;25(19):10501. doi: 10.3390/ijms251910501.
Monogenic defects of beta cell function refer to a group of rare disorders that are characterized by early-onset diabetes mellitus due to a single gene mutation affecting insulin secretion. It accounts for up to 5% of all pediatric diabetes cases and includes transient or permanent neonatal diabetes, maturity-onset diabetes of the young (MODY), and various syndromes associated with diabetes. Causative mutations have been identified in genes regulating the development or function of the pancreatic beta cells responsible for normal insulin production and/or release. To date, more than 40 monogenic diabetes subtypes have been described, with those caused by mutations in and genes being the most prevalent. Despite being caused by a single gene mutation, each type of monogenic diabetes, especially MODY, can appear with various clinical phenotypes, even among members of the same family. This clinical heterogeneity, its rarity, and the fact that it shares some features with more common types of diabetes, can make the clinical diagnosis of monogenic diabetes rather challenging. Indeed, several cases of MODY or syndromic diabetes are accurately diagnosed in adulthood, after having been mislabeled as type 1 or type 2 diabetes. The recent widespread use of more reliable sequencing techniques has improved monogenic diabetes diagnosis, which is important to guide appropriate treatment and genetic counselling. The current review aims to summarize the latest knowledge on the clinical presentation, genetic confirmation, and therapeutic approach of the various forms of monogenic defects of beta cell function, using three imaginary clinical scenarios and highlighting clinical and laboratory features that can guide the clinician in reaching the correct diagnosis.
单基因β细胞功能缺陷是一组罕见疾病，其特征为单个基因突变导致胰岛素分泌异常，从而引发早发糖尿病。这类疾病约占所有儿童糖尿病病例的 5%，包括暂时性或永久性新生儿糖尿病、青年发病的成年型糖尿病（MODY）以及各种与糖尿病相关的综合征。导致这些疾病的致病突变已在调控胰腺β细胞发育或功能的基因中被发现，这些基因对于正常胰岛素的产生和/或分泌至关重要。迄今为止，已经描述了超过 40 种单基因糖尿病亚型，其中由 和 基因突变引起的亚型最为常见。尽管单基因糖尿病由单个基因突变引起，但每种类型的单基因糖尿病，尤其是 MODY，即使在同一家庭的成员中，也可能表现出不同的临床表型。这种临床异质性、其罕见性以及与更常见类型糖尿病的某些特征的相似性，使得单基因糖尿病的临床诊断颇具挑战性。事实上，一些 MODY 或综合征性糖尿病患者在成年后才被准确诊断，此前他们被误诊为 1 型或 2 型糖尿病。最近，更可靠的测序技术得到了广泛应用，从而改善了单基因糖尿病的诊断，这对于指导适当的治疗和遗传咨询非常重要。本综述旨在通过三个虚构的临床病例，总结目前对各种单基因β细胞功能缺陷的临床表现、基因确认和治疗方法的最新认识，并强调可以帮助临床医生做出正确诊断的临床和实验室特征。
