MON-879 - Rare Coexistence of Klinefelter Syndrome and 17Q12 Microdeletion (MODY-5) in A Patient with Uncontrolled Diabetes

Background:
To date, no cases of co-occurring Klinefelter syndrome and 17q12 microdeletion have been reported. These distinct genetic conditions lead to separate endocrinologic disorders, including hypogonadism and diabetes.

Clinical Presentation:
A 32-year-old man with exocrine pancreatic insufficiency of unknown etiology and poorly controlled diabetes with recurrent hypo- and hyperglycemia, complicated by necrotizing fasciitis of the right leg status post amputation, proliferative retinopathy, and neuropathy, was referred for genetic evaluation to determine etiology of pancreatic insufficiency. Chronic pancreatitis gene panel revealed an incidental gain of the X chromosome. Chromosomal microarray confirmed 47,XXY, consistent with Klinefelter syndrome, and identified a pathogenic 17q12 microdeletion involving HNF1B, associated with maturity-onset diabetes of the young type 5 (MODY-5).
The patient was subsequently referred to endocrinology for management of Klinefelter syndrome and uncontrolled diabetes. At presentation, HbA1c was 9.3% ( < 5.7%). Metformin was discontinued due to gastrointestinal intolerance, basal–bolus insulin doses were adjusted, and continuous glucose monitor was set up. Diabetes autoantibodies (GAD-65, IAA, IA-2A, ZnT8A) were negative.
Hormonal evaluation demonstrated primary hypogonadism with FSH 62.29 mIU/mL (1.27–19.26), LH 79.47 mIU/mL (1.24–8.62), total testosterone 197 ng/dL (250–1100), free testosterone 30 pg/mL (46–224), bioavailable testosterone 62.9 ng/dL (110–575), albumin 4.6 g/dL (3.6–5.1), and SHBG 24.7 nmol/L (10–50). DEXA scan showed normal BMD at all sites: lumbar spine L1–L4 1.208 g/cm² (T −0.2, Z −0.2), left femoral neck 1.122 g/cm² (T 0.4, Z 0.5), and non-dominant radius (33%) 1.049 g/cm² (T 0.6, Z 0.6). Initiation of testosterone therapy is currently delayed due to loss of insurance coverage and need for financial assistance.

Conclusion:
This case describes the co-occurrence of Klinefelter syndrome and 17q12 microdeletion in a patient with uncontrolled diabetes and pancreatic insufficiency. 17q12 microdeletion is associated with multiple endocrine disorders, including MODY-5 and hyperparathyroidism, with marked variability in penetrance and severity even among affected family members, necessitating long-term endocrine surveillance. Recognition of multiple genetic etiologies is essential for individualized endocrinologic management, particularly for diabetes and hypogonadism, and highlights the importance of comprehensive genetic evaluation in atypical presentations.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*