S5389 Sclerosing Cholangitis and Polycythemia in a Patient With Down Syndrome: A Case Highlighting Autoimmune and Hematologic Interplay

Introduction: Down syndrome (trisomy 21) is associated with a broad range of comorbidities, including congenital heart disease, gastrointestinal anomalies, and increased susceptibility to autoimmune conditions. Among these, autoimmune liver diseases such as sclerosing cholangitis (SC) may be underrecognized. Additionally, polycythemia is a relatively common hematologic finding in neonates with Down syndrome and may persist or recur later due to hypoxia or other factors. Case Description/Methods: We present a 28-year-old man with Down syndrome and vasovagal syncope who was referred for evaluation of abnormal liver enzymes discovered incidentally during routine testing. He denied fatigue, pruritus, or recent infections, and had no history of biliary surgery or recent antibiotic use. Labs showed alanine aminotransferase 88 U/L, alkaline phosphatase 227 U/L, gamma-glutamyl transferase 537 U/L, hemoglobin 17.4 g/dL, hematocrit 50.1%, and elevated gamma globulins. Autoimmune serologies were negative for antinuclear antibody and antimitochondrial antibodies but positive for anti-smooth muscle antibodies at 1:160. Iron saturation was 5%, and ceruloplasmin was normal. FibroScan revealed F0–F1 fibrosis (LSM 4.1), and magnetic resonance cholangiopancreatography showed no biliary obstruction. A liver biopsy, obtained due to suspicion for antimitochondrial antibody-negative primary biliary cirrhosis, revealed portal fibrosis with concentric “onion-skin” fibrosis around septal and interlobular bile ducts, consistent with sclerosing cholangitis. No bile duct loss or significant inflammation was noted. IgG4 was normal. He is currently managed as having primary SC and is being evaluated for secondary causes of polycythemia. Discussion: Individuals with Down syndrome are at increased risk for autoimmune diseases including autoimmune thyroiditis, celiac disease, and type 1 diabetes, likely due to immune dysregulation. SC, particularly primary SC (PSC), is a chronic liver disease involving progressive bile duct inflammation and fibrosis, often linked to inflammatory bowel disease. Secondary SC arises from known insults such as infection, ischemia, or toxins. In this patient, immune dysfunction may underlie SC pathogenesis. Polycythemia in Down syndrome may stem from chronic hypoxia, obstructive sleep apnea, or inflammation-induced erythropoiesis. This case highlights the need for heightened awareness of autoimmune liver diseases and hematologic abnormalities such as polycythemia in adults with Down syndrome. Understanding the immune-genetic link may offer insights into management and surveillance in this unique population.