A Rare Monogenic Metabolic Syndrome from a DYRK1B Variant: Management Challenges and Insights

Metabolic syndrome is traditionally regarded as a polygenic disorder; however, rare monogenic forms have been described.We report a 21-year-old woman with a heterozygous DYRK1B variant presenting with an abdominal obesity-metabolic syndrome 3 (AOMS3)-like phenotype, initially misdiagnosed as polycystic ovarian syndrome.Genetic analysis revealed a c.755G>A (p.R252H) variant in the DYRK1B gene, associated with an AOMS3-like phenotype.Novel features included hyperandrogenism, severe hypertriglyceridemia, and absence of prominent adipogenesis, thereby expanding the phenotypic spectrum of DYRK1Bassociated metabolic disease.Notably, this is one of the few reports describing longitudinal metabolic improvement over 6 months following SGLT2 inhibitor therapy in DYRK1Bassociated AOMS3 after inadequate control with conventional oral antidiabetic therapy.