During our posting in Pediatric Department, we need to take history and do a clinical examination of related organ systems. One day, we had a class on the Gastrointestinal and Hepatobiliary systems. For that, we were given a case of a child with suspected Wilson’s disease. We approached the Child as a patient with liver disease with jaundice. Since we had limited time, we could not go through all the theories of Wilson's disease, and even multiple investigations were done, which left us unsure about the diagnosis. Hence, we presented the history and clinical examination of the Gastrointestinal and hepatobiliary systems. After that, our teacher asked for any findings related to the Nervous system or ophthalmological system and a confirmatory diagnosis of Wilson’s disease. We had no clue at that time. Those questions made me more curious about the disease. So, later that day, I went through the topic and I could get why our teacher had asked that question. Wilson’s disease is a multisystem Disease. Diagnosis is difficult and it involves blood tests, urine tests, and a liver biopsy along with the clinical evaluation.
Wilson disease is a rare, chronic disorder characterized by copper accumulation in organs and tissues that, if left untreated, may result in liver, neurologic, and psychiatric symptoms that progress over time. Wilson disease is an autosomal recessive condition caused by a mutation in the Wilson disease protein (ATP7B) gene. (1)
Pathogenesis of Wilson’s disease
In Wilson’s disease, there is a defect on the ATP7B gene on chromosome 13 which codes for p-type adenosine triphosphate. It is involved in the excretion of excess copper into the bile by incorporation of copper with ceruloplasmin (Cu++ binding protein). Bound Cu++ in the blood is non-toxic.
The gene defect in Wilson’s disease affects copper transport system that produces dual defects: decreased incorporation of copper into ceruloplasmin in the liver and decreased excretion of copper in bile. Accumulation of copper in the liver increases the formation of hydroxyl free radicals causing damage to hepatocytes. In a few years, unbound copper is released from liver into the circulation where it damages brain, cornea, kidneys, and other tissues. Defective copper incorporation into apo ceruloplasmin leads to excess catabolism and low blood levels of ceruloplasmin. (1, 2)
Clinical Features (3)
Symptoms usually are related to the brain and liver which includes:
Chronic liver disease, cirrhosis of liver: Age at presentation is usually >1-2 years.
- Kayser-Fleischer (KF) ring in the cornea due to the deposition of Cu++ in the descemet membrane.
- Cataract: Sunflower cataract
- Basal ganglia damage: Abnormal movements, tremors, seizures
- Psychiatric manifestations
First feature of brain damage noted in children with Wilson’s disease is Deterioration of school performance. Childhood onset presents with chronic liver disease. Adult onset presents usually with neurological manifestation. The onset of neurologic symptoms is usually in the second and less often in the third decade, rarely beyond that time. In all instances, the initial event is deposition of copper in the liver, leading to acute or chronic hepatopathy and eventually to multilobular cirrhosis and splenomegaly. (2)
Doctors diagnose Wilson disease based on medical and family history, a physical examination, ophthalmological examination, blood tests, and urine tests. Liver biopsy and imaging tests are also important for diagnosis.
- Blood tests: Serum ceruloplasmin decreased, Abnomal Liver enzymes ( Alanine Transaminase, Aspartate Transaminase)
- 24-hour urine collection test: Urine Cu++
- Liver biopsy: macrovascular steatosis & Mallory-Hyaline bodies
- Imaging tests: Magnetic Resonance Imaging, Computed Tomography Scan
Assessment of Cu++ levels in the liver tissue increased (250 microgram/gram weight of the liver)
Aim: Decrease the Cu++ levels in the body by decreasing intake.
Early diagnosis and treatment can reduce or prevent organ damage.
Diet change: Avoid foods that are high in copper.
1. Cu++ chelating agents:
It removes copper from the body
- D-Penicillamine : Drug of Choice in children
· Chronic use of D-Penicillamine leads to a deficiency of Vitamin B6. Hence, the patient is supplemented with Vitamin B6 which prevents optic neuritis.
- Induces the production of metallothionein which inhibits the absorption of Cu++ from the intestine
Chronic Liver Disease/Cirrhosis: Liver transplantation
People who have Wilson's disease need lifelong treatment and acute liver failure may occur if patient suddenly stops treatment. Timely follow-up and necessary investigations are required to evaluate the efficacy of treatment.
1. Chaudhry HS, Anilkumar AC. Wilson Disease. [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441990/
2. Maurice Victor, Allan HR : Hepatolenticular degeneration (Wilson’s disease, Westphal Strumpell Pseudosclerosis) in Principle of Neurology, 7th edition, Westphal, Strumpell 1898, pp 1026-30.
3. Davidson SS et al: Wilson’s disease in Principles And Practice Of Internal Medicine, 21st edition, JD Collier and G.Webster, 2010, pp960-962
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