16-OR: Endocrine Manifestations of Pediatric HNF1B-MODY (MODY 5)

Abstract

Objective: Mutations in hepatocyte nuclear factor 1B (HNF1B), are often identified based on a history of renal disease and diabetes mellitus, but other endocrine manifestations including dyslipidemia and hyperparathyroidism have not been well-defined in the literature. Given HNF1B-MODY is rare, there have been few case series defining the disease spectrum. This study analyzes the clinical characteristics of HNF1B-related endocrine disorders in 9 pediatric patients identified at a single pediatric tertiary care center. Methods: Data was collected through the Atypical Diabetes Registry and Biorepository at the Children’s Hospital of Philadelphia. Results: Of the 9 pediatric patients with HNF1B mutations or deletions, 7/9 (78%) have diabetes mellitus, 8/9 (89%) have renal disease, 8/9 (89%) have dyslipidemia, and 5/9 (55%) have hyperparathyroidism. Over half (55%) initially presented with diabetes mellitus, while the remaining 45% were diagnosed either based on family history or a genetic workup secondary to renal disease. No patients presented with diabetic ketoacidosis and only two presented with ketosis. Of the 4/9 with previously identified HNF1B-mutations, two have subsequently developed diabetes mellitus. Lipid profiles demonstrated: 7/9 with total cholesterol >170 mg/dL, 8/9 with triglycerides >100 mg/dL, 3/9 with LDL > 110 mg/dL and 3/9 with HDL < 40 mg/dL. In regards to calcium homeostasis, 55% have an elevated PTH (>65 pg/mL) with high-normal calcium levels. Autism spectrum disorder was diagnosed in 3/9 patients (2 with 17q12 deletion and 1 with HNF1B mutation). Conclusion: This study represents one of the largest series of pediatric patients with HNF1B-MODY at a single center. The majority of patients have had progressively declining beta-cell function resulting in diabetes mellitus. Nearly all had elevated lipids with hypertriglyceridemia predominating. Over half of the patients had elevated PTH levels preceding the decline in renal function concerning for primary hyperparathyroidism. Disclosure M. E. Craven: None. V. Bamba: None. A. C. Calabria: None. S. E. Pinney: None.