2424 Hepato to the Metal: The Irony of Wilson Disease

Abstract

INTRODUCTION: Wilson Disease (WD) is a disorder of copper metabolism resulting in the accumulation of copper within the liver and other organs. It is caused by mutations in the ATP7B gene, which codes for a copper transport protein in the liver. The absent or compromised ATP7B protein not only causes copper accumulation in the liver but also reduces the amount of circulating ceruloplasmin. Hemochromatosis describes an iron overload syndrome that can be either primary or secondary, the latter carrying a broad differential. We describe a case of a patient with newly diagnosed WD with concomitant iron overload. CASE DESCRIPTION/METHODS: 30-year-old otherwise healthy male presents with eight-month history of persistently elevated LAEs (liver associated enzymes). Eight months ago his ALT was 127 U/L and his AST was 67 U/L with all other elements of his liver function being normal. He uses NSAIDs once a month for neck and low back pain. He denies supplement use and does not consume alcohol. No known family history of metabolic liver disease. Review of systems was otherwise normal including no neuropsychiatric symptoms Physical exam was normal. LAEs at current presentation were ALT of 155 U/L and AST of 75 U/L, with normal total bilirubin and ALP. He had new thrombocytopenia of 143,000/μL. INR was normal. Infectious, autoimmune, and metabolic serologic testing were all unremarkable except ceruloplasmin <3.0 mg/dL and ferritin of 646 ng/mL. Iron (70 μg/dL) and iron saturation (24.1%) were normal. Concern for WD prompted a 24-hour urine copper collection. His 24 hour urine copper level was elevated (113 μg). Slit-lamp exam was normal. Liver ultrasound was unremarkable. Vibration controlled transient elastography score was elevated (11.8 kPa, IQR/med 8%). Liver biopsy revealed bridging fibrosis with negative copper staining, but iron stain showing moderate hepatocellular iron deposition. DISCUSSION: In addition to its copper carrying property, ceruloplasmin has ferroxidase activity. Hypoceruloplasminemia found in WD consequently leads to decreased amount of circulating iron and increased iron stores, leading to iron accumulation in the liver. Although primary hemochromatosis should be considered in the evaluation of patients with WD with evidence of iron overload, it is important to realize that iron overload can also be a second order effect of WD. Iron indices should be monitored in patients with WD, particularly during chelation therapy, as ceruloplasmin levels may further decrease and worsen iron accumulation.