S2635 Abnormal Liver Enzymes Attributed to HNF-1b Associated Disease

Abstract

Introduction: Hepatocyte nuclear factor 1 beta (HNF-1b) associated diseases are genetic conditions caused by an error in the HNF1b gene. This gene regulates early development of organs such as the kidney, genital tract, and pancreas. Common signs/symptoms include kidney findings like cysts, mature onset of diabetes at a young age (MODY), genital abnormalities, as well as abnormal pancreas/liver function. We present a case of abnormal liver enzymes secondary to HNF-1b associated disease. Case Description/Methods: A 22-year-old man was referred for abnormal liver enzymes and suspected NAFLD. Past medical history included surgery for an undescended testicle at age 6 and new onset DM with relative weight loss. Due to DM, weight loss, and a family history of pancreatic cancer he was evaluated by GI and had labs in 1/2020 showing ALK PHOS (254 U/L), AST (98 U/L), ALT (251 U/L), and total bilirubin (1.4 mg/L). MRI/MRCP in 3/2020 was overall unremarkable and upper EUS 6/2020 showed echogenic liver and increased fullness of the pancreas with non-hyperechoic stranding throughout. Detailed serologic evaluation was without specific abnormalities other than ongoing elevated liver enzymes in a mixed pattern. He had a liver biopsy in 1/2021, in which native bile ducts were absent in < 50% of portal tracts, while other portal tracts contained small ducts relative to size of the tract. Portal vein abnormalities were noted including atrophy and fragmentation. No features of NAFLD or chronic liver diseases. He underwent a genetic cholestasis panel showing a heterozygous ∼1.51 Mb deletion that was pathogenic for HNF-1b associated disease. He has been referred to a genetic counselor and maintains follow up with his specialty teams. Discussion: The HNF1B gene is associated with functional and transcriptional regulation in hepatobiliary, pancreatic B-cells, and urogenital tract tissues. Pathogenic deficiencies are related to point mutations or deletions. The combination of MODY 5 diabetes plus renal cysts or urogenital abnormality has led this finding to be called RCAD (renal cysts and diabetes). There have been case reports with classic syndrome plus varying hepatobiliary findings. To our knowledge, this is the first case of HNF-1B associated disease without the classic finding of renal pathology. It is suggested that for young patients with early onset of diabetes with abnormal hepatobiliary and/or pancreatic testing, HNF-1B disease be considered in the differential diagnosis.Figure 1.: Prevention Genetics - Cholestasis Panel Molecular Genetic Report.