Wilson Disease - Cards (ver10)

Summary / Overview

• Wilson disease, also called hepatolenticular degeneration, is a rare autosomal recessive copper metabolism disorder caused by pathogenic mutations in ATP7B
• Defective biliary copper excretion leads to progressive copper accumulation, first in the liver and later in the brain, cornea, and other tissues
• Major clinical involvement is hepatic, neurologic, and psychiatric; ocular findings such as Kayser-Fleischer rings are important clues
• Children often present with liver disease, while neurologic and psychiatric manifestations become more prominent in later years
• If untreated, the disease may progress to cirrhosis, liver failure, disabling neurologic disease, or death
• Diagnosis is based on clinical suspicion supported by ceruloplasmin, copper studies, ocular examination, and sometimes liver biopsy or genetic testing
Wilson disease is a multisystem copper storage disorder in which failure of normal copper excretion causes toxic accumulation in the liver, brain, cornea, and other organs. It commonly presents with hepatic disease in childhood and neurologic or psychiatric manifestations later, and it is one of the important treatable inherited liver disorders.

Etiology

Wilson disease is an autosomal recessive disorder caused by pathogenic mutations in the ATP7B gene on chromosome 13q. ATP7B encodes a copper-transporting ATPase located mainly in the trans-Golgi network of hepatocytes, where it helps incorporate copper into ceruloplasmin and excrete excess copper into bile. More than 300 mutations have been described, and many patients are compound heterozygotes, carrying two different mutant alleles.
Because biliary excretion is the major route of copper elimination, defective ATP7B function leads to progressive copper retention in the liver. Initially, excess copper accumulates in hepatocytes; later it spills into the bloodstream and deposits in other organs, especially the brain and cornea. Copper excess promotes free radical generation and oxidative injury, leading to damage of proteins, lipids, and cellular organelles. Early ultrastructural injury is often seen in mitochondria, nuclei, and peroxisomes.

Pathogenesis

Wilson disease results from defective ATP7B function, causing failure of normal hepatic copper handling. Copper cannot be properly incorporated into ceruloplasmin or excreted into bile, so it first accumulates in the liver and later spills into the bloodstream, depositing in other organs, especially the brain, eyes, and kidneys.
Excess free copper generates reactive oxygen species and oxidative injury, damaging hepatocytes and leading to hepatitis, fibrosis, cirrhosis, and sometimes liver failure. Ceruloplasmin is low because copper-free ceruloplasmin is unstable and rapidly degraded. In hepatic Wilson disease, serum transaminases may rise, while alkaline phosphatase is often low or inappropriately normal; jaundice may be worsened by hemolysis.
Once released into the circulation, free copper deposits in extrahepatic tissues. In the brain, especially the basal ganglia, it causes movement disorders, neuropsychiatric symptoms, and cognitive changes. In the cornea it produces Kayser-Fleischer rings, and in the lens it may cause sunflower cataracts. Copper-induced oxidative injury to erythrocytes can cause intravascular hemolysis with indirect hyperbilirubinemia, while renal tubular toxicity may produce kidney involvement.

Symptoms

Hepatic symptoms
• Abdominal discomfort or distension
• Fatigue
• Nausea, vomiting, poor appetite
• Leg swelling or ascites in advanced disease
Neurologic symptoms
• Tremor
• Slowness and stiffness
• Abnormal involuntary movements
• Unsteady gait / poor coordination

Signs

Hepatic signs
Neurologic signs
Ocular signs
Hemolytic / systemic signs

Wilson disease is an autosomal recessive disorder caused by pathogenic mutations in the ATP7B gene on chromosome 13q. ATP7B encodes a copper-transporting ATPase located mainly in the trans-Golgi network of hepatocytes, where it helps incorporate copper into ceruloplasmin and excrete excess copper into bile. More than 300 mutations have been described, and many patients are compound heterozygotes, carrying two different mutant alleles.

Because biliary excretion is the major route of copper elimination, defective ATP7B function leads to progressive copper retention in the liver. Initially, excess copper accumulates in hepatocytes; later it spills into the bloodstream and deposits in other organs, especially the brain and cornea. Copper excess promotes free radical generation and oxidative injury, leading to damage of proteins, lipids, and cellular organelles. Early ultrastructural injury is often seen in mitochondria, nuclei, and peroxisomes.

References

PDF

PMC

2026-04-01 13:48:13

PDF

https://clinic.drsankaran.org/refseq_atlas/gene.php?q=ATP7B

2026-03-30 18:00:11

Wilson disease results from defective ATP7B function, causing failure of normal hepatic copper handling. Copper cannot be properly incorporated into ceruloplasmin or excreted into bile, so it first accumulates in the liver and later spills into the bloodstream, depositing in other organs, especially the brain, eyes, and kidneys.

Excess free copper generates reactive oxygen species and oxidative injury, damaging hepatocytes and leading to hepatitis, fibrosis, cirrhosis, and sometimes liver failure. Ceruloplasmin is low because copper-free ceruloplasmin is unstable and rapidly degraded. In hepatic Wilson disease, serum transaminases may rise, while alkaline phosphatase is often low or inappropriately normal; jaundice may be worsened by hemolysis.

Once released into the circulation, free copper deposits in extrahepatic tissues. In the brain, especially the basal ganglia, it causes movement disorders, neuropsychiatric symptoms, and cognitive changes. In the cornea it produces Kayser-Fleischer rings, and in the lens it may cause sunflower cataracts. Copper-induced oxidative injury to erythrocytes can cause intravascular hemolysis with indirect hyperbilirubinemia, while renal tubular toxicity may produce kidney involvement.

Hepatic signs

• Hepatomegaly

• Jaundice

• Splenomegaly

• Ascites

• Stigmata of chronic liver disease in advanced cases

Neurologic signs

• Tremor

• Rigidity

• Dystonia

• Dysarthria

• Ataxia / abnormal gait

• Bradykinesia or other extrapyramidal signs

Ocular signs

• Kayser-Fleischer ring

• Sunflower cataract

Hemolytic / systemic signs

• Pallor

• Icterus

The most characteristic examination finding is the Kayser-Fleischer ring, which represents copper deposition in Descemet’s membrane of the cornea and is best detected by slit-lamp examination. Common examination targets also include evidence of liver disease and neurologic extrapyramidal findings.

• Wilson disease, also called hepatolenticular degeneration, is a rare autosomal recessive copper metabolism disorder caused by pathogenic mutations in ATP7B

• Defective biliary copper excretion leads to progressive copper accumulation, first in the liver and later in the brain, cornea, and other tissues

• Major clinical involvement is hepatic, neurologic, and psychiatric; ocular findings such as Kayser-Fleischer rings are important clues

• Children often present with liver disease, while neurologic and psychiatric manifestations become more prominent in later years

• If untreated, the disease may progress to cirrhosis, liver failure, disabling neurologic disease, or death

• Diagnosis is based on clinical suspicion supported by ceruloplasmin, copper studies, ocular examination, and sometimes liver biopsy or genetic testing

• Treatment includes copper chelation, zinc therapy, dietary copper restriction, and liver transplantation in advanced cases

• Early diagnosis and lifelong treatment can markedly improve outcome

Wilson disease is a multisystem copper storage disorder in which failure of normal copper excretion causes toxic accumulation in the liver, brain, cornea, and other organs. It commonly presents with hepatic disease in childhood and neurologic or psychiatric manifestations later, and it is one of the important treatable inherited liver disorders.

Hepatic symptoms

• Abdominal discomfort or distension

• Fatigue

• Nausea, vomiting, poor appetite

• Leg swelling or ascites in advanced disease

Neurologic symptoms

• Tremor

• Slowness and stiffness

• Abnormal involuntary movements

• Unsteady gait / poor coordination

• Speech difficulty

• Swallowing difficulty

Psychiatric / cognitive symptoms

• Behavioral change

• Mood change, depression, anxiety

• Poor concentration / cognitive decline

note: Kayser-Fleischer ring is better placed under signs, not symptoms, because it is an examination finding rather than a symptom. Neurologic and psychiatric manifestations are well recognized in current reviews, while hepatic presentation is often prominent in childhood