Monogenic diabetes in children: An underdiagnosed and poorly managed clinical dilemma

Abstract

Monogenic diabetes, constituting 1%-2% of global diabetes cases, arises from single gene defects with distinctive inheritance patterns. Despite over 50 ass-ociated genetic disorders, accurate diagnoses and management of monogenic diabetes remain inadequate, underscoring insufficient clinician awareness. The disease spectrum encompasses maturity-onset diabetes of the young (MODY), characterized by distinct genetic mutations affecting insulin secretion, and neonatal diabetes mellitus (NDM) – a heterogeneous group of severe hyperglycemic disorders in infants. Mitochondrial diabetes, autoimmune monogenic diabetes, genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape. A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of MODY. NDM diagnosis warrants immediate molecular genetic testing for infants under six months. Identifying these genetic defects presents a unique opportunity for precision medicine. Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes. Identification and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of diabetes. The clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.