BBS10-related Bardet-Biedl syndrome with an atypical presentation of diabetes mellitus: A case report.

Abstract

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive ciliopathy characterized by extensive clinical heterogeneity, which often complicates its diagnosis. The present study reported the case of a 31-year-old woman who presented with longstanding, poorly controlled type 2 diabetes mellitus and its associated complications. The patient exhibited classic features including Class I obesity, retinal dystrophy, postaxial polydactyly, renal dysfunction and hypergonadotropic hypogonadism. A definitive diagnosis was established through whole-exome sequencing, which identified compound heterozygous pathogenic variants in the BBS10 gene (a nonsense mutation, p.Arg256* and a missense mutation, p.Gly180Glu). This case is novel in presenting with adult-onset diabetes as the primary complaint, highlighting the necessity of including BBS in the differential diagnosis of patients with early-onset metabolic disorders and multisystem involvement. Of note, the patient's glycemic control improved after treatment with a glucagon-like peptide-1 receptor agonist (semaglutide). This observation provides important longitudinal evidence suggesting a promising therapeutic strategy for managing metabolic dysfunction in BBS, potentially by engaging residual G-protein-coupled receptor signaling pathways despite underlying ciliary defects.