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Type 2 Diabetes in a Patient With IMAGe Syndrome Secondary to Polymerase Epsilon Pathogenic Variants

Year: 2025

Type: article

Abstract: The authors present a case of a 22-year-old female with a history of intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies syndrome (IMAGe) secondary to pathogenic variants in the polymerase epsilon (POLE) gene who was newly diagnosed with type 2 diabetes. The patient was noted on routine lab work to have elevated blood glucose, and subsequent laboratory analysis revealed a hemoglobin A1c of 8.9% with normal serum insulin concentrations and negative autoimmune evaluation. She did not have physical exam findings or stigmata of insulin resistance. A continuous glucose monitor revealed significant postprandial hyperglycemia. She was initially treated with prandial insulin and was later transitioned to oral sitagliptin due to adherence and administration difficulties. To the best of our knowledge, this is one of the first patients with POLE-mediated IMAGe syndrome to be diagnosed with type 2 diabetes. Given the presence of adrenal insufficiency in this population and the lifelong need for glucocorticoid therapy, special care should be taken when dosing glucocorticoids to reduce the risk of the patient developing insulin resistance. Further research is needed to determine if type 2 diabetes is part of the phenotype for these genetic variants and to elucidate the associated underlying pathophysiology.

Source: JCEM Case Reports

DOI: 10.1210/jcemcr/luaf132

Authors: Andrew Horvit, Neha Mulpuri, Sasan Mirfakhraee, Perrin C White, Jessica Abramowitz

Institutions: The University of Texas Southwestern Medical Center, Columbia University Irving Medical Center, Columbia University

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $930