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

BACKGROUND

Metabolic syndrome is typically polygenic; however, rare monogenic forms such as DYRK1B-associated abdominal obesity-metabolic syndrome 3 (AOMS 3) exist. We report a case with an AOMS 3-like phenotype and highlight novel features and treatment response.

CASE REPORT: A 21-year-old woman with metabolic syndrome was initially misdiagnosed as polycystic ovarian syndrome. She had abdominal obesity, hyperglycemia, hypertriglyceridemia, and hyperandrogenism. Genetic analysis revealed a heterozygous DYRK1B c.755G>A (p.R252H) variant. She lacked prominent adipogenesis. Due to inadequate control with conventional oral antidiabetic therapy, sodium glucose co-transporter 2 (SGLT2) inhibitor was initiated, leading to metabolic improvement over 6 months.

DISCUSSION: This case expands the phenotypic spectrum of DYRK1B-associated AOMS 3 by demonstrating hyperandrogenism, severe hypertriglyceridemia, and absence of marked adipogenesis. It also suggests a potential therapeutic role of SGLT2 inhibitors in such patients.

CONCLUSION

DYRK1B variants should be considered in young patients with atypical metabolic syndrome. SGLT2 inhibitors may provide benefit when conventional therapy is inadequate.