Clinical profile of monogenic diabetes: A case series from a single South Indian diabetes clinic

Monogenic diabetes mellitus (MDM) represents a diverse group of uncommon form of diabetes. Based on the number of reported cases in literatures, it appears that the detection rate of MDM, even in specialized diabetes centers, remains low. This case series provides a comprehensive overview of different MDM cases observed at a single diabetes center, focusing on their clinical features, diagnostic challenges, and management considerations.

We identified 10 cases of MDM by conducting genetic analysis of 77 youth-onset diabetes cases clinically suspected to be MDM. Among these, there were 2 cases of neonatal diabetes mellitus (NDM) [a heterozygous mutation p.Arg825Trp in the ABCC8 gene (transient NDM) and a heterozygous mutation in p.Asp212Tyr in the ABCC8 gene (permanent NDM)], 3 cases of HNF4A MODY (MODY)-1 [a heterozygous promoter mutation 79C/T in the HNF4A gene, a novel heterozygous missense variant in exon 8 of the HNF4A gene that results in the amino acid substitution of serine for arginine at codon 976 (p.Arg326Ser), and a heterozygous mutation p. Arg333Cys in exon 8 of the HNF4A gene], and 4 cases of maternally inherited diabetes and deafness (MIDD) [heteroplasmic missense mutation in the MT-TL1 position (m.3243A>G) encoding for the leucine transfer RNA].

This case series highlights that MDM can be effectively identified in diabetes clinics through careful clinical evaluation and targeted genetic testing. Early detection allows for personalized treatment strategies, optimizing glycemic control, and pre-empt, prevent, or modify associated clinical features to improve patient outcomes.