Liver & intrahepatic bile ducts
Metabolic diseases
Wilson disease
Author: Komal Arora, M.D.
Topic Completed: 1 April 2012
Minor changes: 9 March 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Wilson disease[TI] liver[TI]
Table of Contents
Definition / general | Pathophysiology | Clinical features | Diagnosis | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Electron microscopy description | Differential diagnosis | Additional referencesCite this page: Arora K. Wilson disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverwilsonsdisease.html. Accessed August 11th, 2020.
Definition / general
- Also called hepatolenticular degeneration
- Autosomal recessive disorder affecting 1/30,000 people, causing accumulation of toxic levels of copper in tissues / organs, usually liver, brain, eye (Clin Gastroenterol Hepatol 2005;3:726)
Pathophysiology
- Total body copper is 50 - 150 mg; 40% of ingested copper is normally absorbed in stomach and duodenum and transported to liver loosely bound to albumin
- Free copper dissociates and is transferred to hepatocytes, where it is incorporated into an alpha2 globulin to form ceruloplasmin and resecreted into plasma
- 99% of plasma copper is bound to ceruloplasmin
- Senescent ceruloplasmin is endocytosed by the liver, degraded within lysosomes and excreted into bile, which is the primary route for copper elimination
- Gene for Wilson disease is ATP7B on #13q, which encodes a transmembrane copper transporting ATPase located on the hepatocyte canalicular membrane, which assists with copper excretion into bile
- Most affected patients are compound heterozygotes with different mutations of ATP7B on each allele that cause defective biliary excretion of copper
- Copper accumulates within the liver, exceeding the capacity for ceruloplasmin binding and causing liver injury
Clinical features
- By age 5 years, nonceruloplasmin bound copper causes acute or chronic liver disease, hemolytic anemia, deposition in putamen with frank psychosis or Parkinsonian symptoms, deposition in cornea, kidneys, bones, joints, parathyroid gland; also increased urinary excretion of copper (which is normally minimal)
- Biochemical determination from liver biopsy (can use formalin fixed tissue, > 250 mcg/g dry weight)
- Serum copper levels are not helpful
Diagnosis
- Serum ceruloplasmin < 20 mg/dl, increased liver copper using rhodamine stain, urinary copper excretion > 50 mcg/24 hours
Case reports
- 8 year old boy with acute liver failure (Case of the Week #388)
Treatment
- Longterm copper chelation therapy with D-penicillamine
- Liver transplantation
Microscopic (histologic) description
- Liver: fatty change with vacuolated nucleus (due to glycogen or water), focal hepatocyte necrosis
- Acute or chronic hepatitis may be present and mimic acute or chronic viral hepatitis
- Chronic hepatitis may have Mallory bodies
- Cirrhosis develops late; usually no / minimal eosinophils or plasma cells
- Note: copper deposition is focal and may not be present on needle biopsies
- Fulminant hepatitis: liver collapse with abundant lipofuscin due to degraded membrane fragments; remaining liver shows low grade disease with fibrosis
- Brain: injury to putamen in basal ganglia
- Eye: Kayser-Fleischer rings (green to brown deposits of copper in Descemet membrane in limbus of cornea)
Microscopic (histologic) images
Case of the Week #388:
Rhodanine stain for copper
Electron microscopy description
- Microvesicular steatosis, glycogen nuclei, copper deposits, mitochondrial enlargement with increased matrical body size, increased matrix density, crystalline inclusions, swollen cristae that are separated due to flocculent material in cyst-like dilations
Differential diagnosis
- Copper accumulation also present in primary biliary cirrhosis, other cholestatic states
Additional references
