P-239: HNF1B-MODY in childhood: phenotypic heterogeneity and longitudinal metabolic course in two kidney transplant recipients
J Postigo, G Lay-Son, A Vogel, P Zambrano, H Jueppner, F GrobAbstract
Introduction
HNF1B-related MODY 5 is a multisystem disorder with renal malformations, pancreatic hypoplasia, progressive kidney disease, and variable diabetes expression. Pediatric post-transplant trajectories remain poorly described.
Objectives
To describe glycemic trajectories before and after kidney transplant in two children with HNF1B-related MODY 5.
Methods
We reviewed clinical, biochemical, genetic, imaging, treatment, and CGM data from two children with HNF1B-related MODY 5 followed at a tertiary center in Santiago, Chile.
Results
Case 1 was a 15-year-old boy with bilateral renal dysplasia, pancreatic hypoplasia without exocrine dysfunction, and de novo HNF1B c.964C>T, p.(Gln322Ter). Pre-transplant HbA1c rose from 5.7% to 6.2%. After kidney transplant from a non-related donor, he received tacrolimus, mycophenolate and prednisone 15 mg/day. One month post-transplant, insulin dose was 0.88 IU/kg/day; CGM showed mean glucose 125 mg/dL, GMI 6.3%, TIR 92%, CV 29.8%. Case 2 was a 9-year-old girl with cystic kidney disease, pancreatic hypoplasia without exocrine dysfunction, and HNF1B c.344G>A, p.(Ser115Asn), predicted to disrupt splicing. She underwent living-related kidney transplant from her father at 6 years. Hyperglycemia appeared during infections and steroid exposure, but persisted after steroid withdrawal under tacrolimus-based low-dose immunosuppression. At 34 months post-transplant, she remained on multiple daily injections (MDI), approximately 0.27 IU/kg/day; HbA1c was 7.8%, 7.3%, and 7.7%. Recent CGM showed mean glucose 171 mg/dL, GMI 7.4%, TIR 65%, TAR 35%, and CV 30.3%.
Conclusions
These cases illustrate heterogeneous diabetes expression after kidney transplant in pediatric HNF1B-related MODY 5. One patient showed slowly progressive pre-transplant dysglycemia and near-target early post-transplant CGM metrics despite high insulin needs; the other had persistent insulin-requiring diabetes despite steroid withdrawal. Metabolic surveillance is warranted before and after kidney transplant.