Wilson's disease

INTRODUCTION:
  • Wilson’s disease is a rare genetic condition that causes copper poisoning in the body.
  • The symptoms of Wilson’s disease vary depending on which organ has copper buildup.
  • Early diagnosis and treatment offer the best outlook for people with Wilson’s disease.
  • Siblings of the diagnosed patient with Wilson disease will be having 25% risk of Wilson disease
ETIOLOGY:
  • A mutation in the ATP7B gene, which codes for copper transportation, causes Wilson’s disease.
  • It is autosomal rececieve trait
SIGNS & SYMPTOMS:
  • The following symptoms may indicate copper accumulation in the liver:

  1. Weakness
  2. Feeling tired
  3. Weight loss
  4. Nausea
  5. Vomiting
  6. Loss of appetite
  7. Itching
  8. Jaundice, or yellowing of the skin
  9. Edema, or the swelling of legs and abdomen
  10. Pain or bloating in the abdomen
  11. Spider angiomas, or visible branch-like blood vessels on the skin
  12. Muscle cramps
Neurological
  • Copper accumulation in the brain can cause symptoms such as:
  1. Memory, speech, or vision impairment
  2. Abnormal walking
  3. Migraines
  4. Drooling
  5. Insomnia
  6. Clumsiness with hands
  7. Personality changes
  8. Changes in mood
  9. Depression
  10. Problems in school
Kayser-Fleischer rings and sunflower cataract
  • Kayser-Fleischer (K-F) rings are abnormal golden-brown discolorations in the eyes that are caused by deposits of excess copper.
  • K-F rings show up in about 97 percent of people with Wilson’s disease.
  • Sunflower cataracts show up in 1 out of 5 people with Wilson’s disease.
  • This is a distinctive multicolored center with spokes that radiate outward.
Other symptoms 
  1.  The buildup of copper in other organs can cause:
  2. Anemia:Due to the large amount of copper released into blood stream in wilson disease anemia occurs 
  3. Bluish discoloration in the nails
  4. Kidney stones
  5. Premature osteoporosis, or lack of bone density
  6. Arthritis
  7. Menstrual irregularities
  8. Low blood pressure
DIAGNOSIS:
  • The gold standard for the diagnosis of Wilson disease is Liver biopsy with quantitative copper assay
  • In patients presenting with hepatic decompensation due to wilson disease, the disease severit is estimated using the Nazer prognostic index 
  • Patients with scores < 7 can be managed with medical therapy. 
  • Patients with scores > 9 should be immediately referred for liver transplantation
  • ISHAK score is used to assess fibrosis in liver biopsy
  • Lille score is used in alcoholic hepatitis to assess the treatment response with steroids
  • Rockall score is used in the setting of nonvariceal GI bleed.
  • Essentials of Diagnosis & Typical Features of Wilson disease:
  1. Acute or chronic liver disease
  2. Deteriorating neurologic status
  3. Kayser-Fleischer rings
  4. Elevated liver copper
  5. Abnormalities in levels of ceruloplasmin and serum and urine copper.
TREATMENT:
  • Treatment often happens in three stages and should last a lifetime.
  1. First stage: 
  2. Remove excess copper from body through chelating therapy. 
  3. Chelating agents include drugs like d-penicillamine and trientine, or Syprine. 
  4. During treatment for Wilson disease with trientine and penicillamine, free serum copper should be kept below 25mcg/dl
Second stage:
  1. Maintain normal levels of copper after removal.
  2. Zinc taken orally as salts or acetate (Galzin) keeps the body from absorbing copper from foods
  3. Nontoxic
  4. Produces a negative copper balance by blocking intestinal absorption of copper
  5. It induces hepatic metallothionein synthesis, which sequesters additional toxic copper
Third stage
  • Maintenance therapy: This includes continuing zinc or chelating therapy and regularly monitoring your copper levels.

Condition DOC
Hepatitis or cirrhosis without decompensation: Zinc
Cirrhosis with decompensation: Trientine and Zinc
Mild - Trientine and Zinc
Moderate - Hepatic transplantation
Severe - Hepatic transplantation
Exam Question
  • Advatage of Zinc treatment in wilson disease is that it's Nontoxic, Produces a negative copper balance by blocking intestinal absorption of copper, induces hepatic metallothionein synthesis, which sequesters additional toxic copper
  • In wilson disease patients with hepatic decompensation the disease severity is assessed using Nazer prognostic index.
  • DOC in Wilson disease with Neurologic/Psychiatric manifestation is Tetrathiomolybdate and zinc
  • Low ceruloplasmin is the diagnostic feature of wilson's disease
  • Siblings of the diagnosed patient with Wilson disease will be having 25% risk of Wilson disease
  • Free copper level is increased in the body however Serum copper level is usually lower than normal in wilsons disease
  • Due to the large amount of copper released into blood stream in wilson disease anemia occurs 
  • Kayser-Fleischer ring will be present in Almost 100 % proportion of patients with neurologic manifestations of wilson disease
  • The gold standard for the diagnosis of Wilson disease is Liver biopsy with quantitative copper assay
  • In a patient with wilson disease related compensated cirrhosis, without evidence of neurologic or psychiatric symptoms the best treatment option is Zinc
  • During treatment for Wilson disease with trientine and penicillamine, free serum copper should be kept below 25mcg/dl
  • Intestinal absorption is increased in Wilson disease
  • Gene responsible for Wilson disease is situated on chromosome no 13
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