S5769 Double Trouble: Liver Transplantation in a Patient With Bardet-Biedl Syndrome and Alpha-1 Antitrypsin Deficiency

Introduction: Bardet-Biedl Syndrome (BBS) is a rare ciliopathic disorder characterized by obesity along with other signs of metabolic syndrome, intellectual disability, retinal dystrophy, polydactyly, cystic kidneys, and hypogonadism. BBS treatment is largely focused on management of metabolic syndrome to prevent various associated complications such as metabolic-dysfunction associated steatohepatitis (MASH), though few cases are documented in the literature. Alpha-1 antitrypsin deficiency is a relatively common disease with highly variable clinical manifestations ranging from minimal biochemical changes to emphysema and liver disease. However, the disease rarely progresses to a degree that necessitates liver transplant. Case Description/Methods: A 29-year-old man with a past medical history of BBS, hypertension, diabetes mellitus, and MASH presented to the emergency room for acutely elevated liver function tests on routine outpatient laboratory testing, and 2 weeks of nausea and vomiting. Physical examination notable for a distended abdomen, bilateral lower extremity edema, jaundice and acanthosis nigricans. Labs significant for aspartate aminotransferase 130, alanine aminotransferase 41, albumin 3.1, total bilirubin 25.5, international normalized ratio 1.6, and platelets 92. Abdominal ultrasound and of abdomen and pelvis was performed, revealing cirrhosis, ascites, and splenomegaly. MRCP was performed and negative for any obstruction. Liver biopsy revealed PAS-positive inclusions in hepatocytes suggesting alpha-1 antitrypsin (A1AT) deficiency, and genotype analysis confirmed PI*MZ heterozygosity. Ultimately, the patient was listed for transplant and received a deceased donor liver. Discussion: AAT deficiency is inherited in an autosomal co-dominant fashion; homozygotes for the Z allele (PI*ZZ) have severe deficiency of AAT. Heterozygotes are largely asymptomatic, with PI*MS genotype usually producing sufficient amounts of AAT, and PI*MZ having a slight increased risk of developing liver or lung disease. Approximately 30% of patients with BBS have hepatobiliary disorders, including liver fibrosis, metabolic dysfunction-associated steatotic liver disease, MASH and cystic dilation of bile ducts. Review of the current literature revealed no documented cases of BBS-associated liver cirrhosis. This case uniquely presents a young patient with decompensated cirrhosis, initially attributed solely to MASH secondary to Bardet-Biedl Syndrome who upon further work-up was found to be PI*MZ genotype, illustrating how interacting factors can synergistically lead to need for transplant.