WILSON’S DISEASE - Human & Disease

WILSON’S DISEASE

 

WILSON’S DISEASE


WILSON’S DISEASE -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain. What Organs Are Affected By Wilson's Disease ? - particularly the liver and brain. What Happens With Wilson's Disease ? Symptoms and Signs: ¤ Symptoms rare before 5 years of age
Wilson's Disease







-(Copper Storage Disease)

-(Hepato-lenticular Degeneration Syndrome)

-(WD)

Who is most at risk for Wilson Disease ?
Risk Factors:


¤ Family history of liver, neurologic, and/or psychiatric disease.


What Is Wilson's Disease Caused by ?

Causes:

Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. 

Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. 

Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain.

WILSON’S DISEASE WILSON’S DISEASE -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain. What Organs Are Affected By Wilson's Disease ? - particularly the liver and brain. What Happens With Wilson's Disease ? Symptoms and Signs: ¤ Symptoms rare before 5 years of age Wilson's Disease -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The







What Organs Are Affected By Wilson's Disease ?

- particularly the liver and brain.


What Happens With Wilson's Disease ?

Symptoms and Signs:

¤ Symptoms rare before 5 years of age

¤ Hepatic disease

° Asymptomatic with biochemical abnormalities

° Chronic hepatitis, with or without fatigue

° Cirrhosis with symptoms & signs of liver failure

° Fulminant hepatitis with or without intravascular hemolysis

¤ Neurologic disease

° Kayser-Fleischer rings in 90–100% with neurologic disease

° Dystonia with rigidity, contractures, bradykinesia, & cognitive impairment

° Tremors & ataxia

° Dysarthria, dyskinesia, & organic personality syndrome

¤ Psychiatric disease

° Symptoms present in almost all patients with neurologic disease

° Early symptoms: subtle behavioral changes, with deterioration of academic or work performance

° Late symptoms: emotional lability, depression, impulsive behavior, personality changes

° Rare: schizophreniform psychosis, anxiety, cognitive impairment

¤ Symptomatic arthropathy

¤ Azure lunulae (blue discoloration of fingernail base)

¤ Abdominal pain related to cholelithiasis.

WILSON’S DISEASE WILSON’S DISEASE -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain. What Organs Are Affected By Wilson's Disease ? - particularly the liver and brain. What Happens With Wilson's Disease ? Symptoms and Signs: ¤ Symptoms rare before 5 years of age Wilson's Disease -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The









How Do You Know If You Have Wilson's Disease ?

(What test confirms Wilson's Disease) ?


Tests:

Basic Tests: Blood
¤ Low serum ceruloplasmin in 90% of all patients & 65–85% of patients with hepatic manifestations with hepatic manifestations cirrhosis.

WILSON’S DISEASE WILSON’S DISEASE -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain. What Organs Are Affected By Wilson's Disease ? - particularly the liver and brain. What Happens With Wilson's Disease ? Symptoms and Signs: ¤ Symptoms rare before 5 years of age Wilson's Disease -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The








What treatment is used for Wilson's Disease ?


Treatment Options:

¤ D-penicillamine: give vitamin B6 also

° Initial therapy: 250–500 mg PO daily; gradually increase to 1,000–1,500 mg daily, in 3–4 divided doses

° Maintenance: 750–1,250 mg daily, in 3–4 divided doses

¤ Trientine

° Initial therapy: 1–2 grams PO daily, in 3–4 divided doses

° Maintenance: 750–1,000 mg daily, in 3–4 divided doses

¤ Zinc salts

° Maintenance: 150 mg PO daily, in 3 divided doses

¤ Ammonium tetrathiomolybdate

° Initial therapy: 120–420 mg per day for 8 weeks

° Maintenance: use zinc salts.

WILSON’S DISEASE WILSON’S DISEASE -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain. What Organs Are Affected By Wilson's Disease ? - particularly the liver and brain. What Happens With Wilson's Disease ? Symptoms and Signs: ¤ Symptoms rare before 5 years of age Wilson's Disease -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The







Side Effects & Contraindications:

 
¤ D-penicillamine

° Side effects: hypersensitivity reaction, bone marrow suppression, proteinuria, lupus-like reaction, myasthenia, may worsen neurologic symptoms, pemphigoid-type skin reaction.

¤ Contraindications

- Absolute: history of penicillamine-related aplastic anemia or agranulocytosis

- Relative: concomitant therapy with gold salts, antimalarial or cytotoxic drugs, oxyphenbutazone, phenylbutazone.

¤ Trientine

° Side effects: sideroblastic anemia, rhabdomyolysis

° Contraindications

Absolute: known hypersensitivity

¤ Zinc salts

° Side effects: gastric intolerance, headache

° Contraindications: none

¤ Ammonium tetrathiomolybdate

° Side effects: bone marrow suppression, elevation of aminotransferases.



follow-up:

During Treatment

¤ With penicillamine and trientine, aim for 24-hour urine copper >250 mcg per day or serum free copper <0.1 mg/L, checking every 3–6 months; with zinc therapy, urine copper usually <150 mcg per day & urine zinc >1,000 mcg per day. CBC & urinalysis every 2 weeks during first 2 months of penicillamine therapy

¤ CBC, AST, and ALT every 2 weeks during therapy with ammonium tetrathiomolybdate

¤ Annual slit-lamp examination.

WILSON’S DISEASE WILSON’S DISEASE -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The copper-transporting ATPase 2 protein is critical for eliminating excess copper from the body; however, variants in the ATP7B gene impair its function and hinder it from properly removing excess copper from the body. Consequently, excessive amounts of copper are built up and can cause damage to organs, particularly the liver and brain. What Organs Are Affected By Wilson's Disease ? - particularly the liver and brain. What Happens With Wilson's Disease ? Symptoms and Signs: ¤ Symptoms rare before 5 years of age Wilson's Disease -(Copper Storage Disease) -(Hepato-lenticular Degeneration Syndrome) -(WD) Who is most at risk for Wilson's Disease ? Risk Factors: ¤ Family history of liver, neurologic, and/or psychiatric disease. What Is Wilson's Disease Caused by ? Causes: Wilson Disease is caused by mutations in the ATP7B gene. This gene supplies instructions to create a protein referred to as copper-transporting ATPase 2, which is involved in transporting copper from the liver to other parts of the body. Copper is necessary for a variety of cellular functions but can become toxic when there is too much. The









complications and prognosis:


¤ Hepatic: occurs at mean age of 8–12 years; 5–30% of patients with Wilson’s present with chronic hepatitis; consider liver transplantation for fulminant hepatitis or decompensated cirrhosis.

¤ Neurologic: often occurs in 2nd to 3rd decades of life; initial presentation in one-third of patients

¤ Psychiatric: occurs in one-third of patients; requires chelation therapy

¤ Acute intravascular hemolysis: presenting feature in up to 15%; often seen with fulminant hepatitis; usually transient

¤ Renal: includes renal tubular acidosis, nephrocalcinosis, hematuria, aminoaciduria; chelation improves renal function.

¤ Symptomatic arthropathy: occurs in 25–50% of all patients, resembling premature osteoarthritis; 50% have osteomalacia, osteoporosis, or both

¤ Cardiac: arrhythmias & cardiomyopathy may develop; rarely clinically evident

¤ Cholelithiasis: pigment & cholesterol gallstones

¤ Malignancy: cholangiocarcinoma, HCC, and adenocarcinoma of

indeterminate origin may develop in 4 -15% of patients, regardless of treatment.


 What is the life expectancy of a person with Wilson's Disease ?  


Prognosis:

¤ Generally excellent in patients compliant optimaly with therapy.

Next Post Previous Post