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Case Reports
. 2025 Jun 10;3(7):luaf132.
doi: 10.1210/jcemcr/luaf132. eCollection 2025 Jul.

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

Andrew Horvit  1 , Neha Mulpuri  2 , Sasan Mirfakhraee  3 , Perrin C White  4 , Jessica Abramowitz  3
Affiliations
Case Reports

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

Andrew Horvit et al. JCEM Case Rep. .

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.

Keywords: IMAGe syndrome; POLE; type 2 diabetes.

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Figures

Figure 1.
Figure 1.
Initial 14-day continuous glucose monitor report following type 2 diabetes diagnosis.
Figure 2.
Figure 2.
Fourteen-day continuous glucose monitor report 3 years following type 2 diabetes diagnosis on metformin and sitagliptin.
See this image and copyright information in PMC

References

    1. Vilain E, Le Merrer M, Lecointre C, et al. IMAGe, a new clinical association of intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. J Clin Endocrinol Metab. 1999;84(12):4335‐4340. - PubMed
    1. Arboleda VA, Lee H, Parnaik R, et al. Mutations in the PCNA-binding domain of CDKN1C cause IMAGE syndrome. Nat Genet. 2012;44(7):788‐792. - PMC - PubMed
    1. Logan CV, Murray JE, Parry DA, et al. DNA polymerase epsilon deficiency causes IMAGe syndrome with Variable immunodeficiency. Am J Hum Genet. 2018;103(6):1038‐1044. - PMC - PubMed
    1. Nakano T, Sasahara Y, Kikuchi A, et al. Novel POLE mutations identified in patients with IMAGE-I syndrome cause aberrant subcellular localisation and protein degradation in the nucleus. J Med Genet. 2022;59(11):1116‐1122. - PMC - PubMed
    1. Kerns SL, Guevara-Aguirre J, Andrew S, et al. A novel variant in CDKN1C is associated with intrauterine growth restriction, short stature, and early-adulthood-onset diabetes. J Clin Endocrinol Metab. 2014;99(10):E2117‐E2122. - PMC - PubMed

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