S5399 Recurrent Hepatic Adenoma Post-Orthotopic Liver Transplant in Heterozygote Glycogen Storage Disease Type Ia: Implications for Genetic and Immune-Mediated Pathways

Introduction: Glycogen storage disease type Ia (GSD-Ia), caused by G6PC mutations, predisposes patients to hepatic adenomas (HCA) in 70%–80% of cases. Liver transplantation (LT) corrects metabolic derangements but carries a 22% risk of HCA recurrence, often linked to genetic drivers like β-catenin (CTNNB1) or HNF1A mutations. This case highlights recurrent HCA in a heterozygote GSD-Ia patient post-LT, underscoring unresolved genetic and immune mechanisms. Case Description/Methods: A 21-year-old man with heterozygous glycogen storage disease type I (GSD-I) underwent orthotopic liver transplant (OLT) in 2010 for multiple hepatic adenomas. He had no history of hepatitis, liver risk factors, or family history of hepatobiliary disease. Pre-transplant genetic testing was inconclusive for GSD but revealed APC and TP53 mutations, suggesting a genetic predisposition to neoplasia. Post-OLT, he experienced early rejection managed with prednisone, followed by alloimmune hepatitis requiring triple immunosuppression, which led to cognitive decline. Liver biopsy showed portal fibrosis and plasma cell-rich interface hepatitis. Surveillance imaging in 2017 revealed 5 small, focal nodular hyperplasia-like liver lesions, stable on follow-up. By 2022, labs showed elevated bilirubin, aspartate aminotransferase, and ammonia, but imaging remained unchanged. In 2024, MRI identified a new 3 cm hepatic mass and 2 smaller lesions, confirmed as recurrent hepatic adenomas on biopsy. Repeat genetic testing confirmed heterozygous GSD-I. This case highlights the complexity of hepatic neoplasms in GSD-I post-OLT, suggesting that genetic predisposition and chronic inflammation may drive recurrence despite metabolic correction, underscoring the need for ongoing surveillance and genetic evaluation. Discussion: Recurrent hepatocellular adenoma post-LT challenges the paradigm of metabolic cure in GSD-Ia. Heterozygosity may permit subclinical glycogen accumulation, while IST and chronic inflammation could drive CTNNB1 activation. The coexistence of APC and TP53 mutations suggests a polygenic predisposition, warranting the use of next-generation sequencing to clarify oncogenic pathways. This case highlights the importance of lifelong surveillance in GSD-Ia patients after liver transplantation, even in the presence of metabolic stability. Genetic and immune-mediated mechanisms may synergize to promote HCA recurrence, necessitating research into targeted therapies and risk stratification.