WILSON’S DISEASE

DONE BY-

ANURADHA ASHOK

CLASS : 12 D

ROLL NO : 23

LIST OF CONTENTS

1.ACKNOWLEDGEMENTS

2.INTRODUCTION

3.HISTORY

4.CAUSES

5.DIAGNOSIS

6.SIGNS AND SYMPTOMS

7.TREATMENT

8.PATTERN OF INHERITANCE

9.CASE STUDY

10.BIBLIOGRAPHY

ACKNOWLEDGEMENTS

I would like to thank the biology department for giving us the opportunity to do such an informative project. I would like to thank my biology teacher for helping us make our project a successful one. I would also like to acknowledge the staff of SQU for providing us the information about the disease and the case study notes. Lastly, I would sincerely like to thank the patient and her guardian for giving us permission to prepare a case study based on her.

2. Introduction-

Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder that prevents the body from getting rid of extra copper. A small amount of copper obtained from food is needed to stay healthy, but too much copper is poisonous. In Wilson disease, copper builds up in the liver, brain, eyes, and other organs. Over time, high copper levels can cause life-threatening organ damage.

The condition is due to mutations in the Wilson disease protein (ATP7B) gene. A single abnormal copy of the gene is present in 1 in 100 people, who do not develop any symptoms (they are carriers). If a child inherits the gene from both parents, they may develop Wilson's disease. About one in 40,000 people get Wilson disease.1 It equally affects men and women. Symptoms usually appear between ages 5 to 35, but new cases have been reported in people aged 2 to 72 years.

Abnormal (above) & Normal gene (below)

3. History- The disease was first discovered by Samuel Alexander Kinnear Wilson (1878-1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. Prof John N. Cumings made the link with copper accumulation in both the liver and the brain in 1948.

Cumings, and simultaneously the New Zealand neurologist Dr Derek Denny-Brown, working in the USA, first reported effective treatment with metal chelator British anti-lewisite in 1951. This treatment had to be injected but was one of the first therapies available in the field of neurology. The first effective oral chelation agent, penicillamine, was discovered in 1956 by the British neurologist Dr John Walshe. Zinc acetate therapy initially made its appearance in the Netherlands, where physicians Schouwink and Hoogenraad used it in 1961 and in the 1970s, respectively, but it was further developed later by Brewer and colleagues University of Michigan.

Wilson described hepatolenticular degeneration in his Gold Medal winning M.D. dissertation of 1912 titled "Progressive lenticular degeneration".[1] He was honored for his research of the disease, and afterwards the disorder became known as "Wilson's disease"

Samuel Alexander Kinnear Wilson

4. Causes- Wilson's disease is a rare inherited disorder, passed in families as a recessive trait. It is caused by a build up of copper in the body. Normally, copper from the diet is filtered out by the liver and released into bile, which flows out of the body through the gastrointestinal tract. People who have Wilson disease cannot release copper from the liver at a normal rate, due to a mutation of the ATP7B gene When the copper storage capacity of the liver is exceeded, copper is released into the

bloodstream and travels to other organs—including the brain, kidneys, and eyes.

The gene defect is believed to result in an abnormal protein within liver cells that binds to copper, retaining it in the liver. Patients with Wilson's disease also frequently have decreased amounts of a protein, called ceruloplasmin, that carries copper through the bloodstream. If both parents carry an abnormal gene for Wilson's disease, there is a 25% chance that each of their children will develop the disorder.

Wilson's disease causes the body to absorb and retain excessive amounts of copper. The copper deposits in the liver, brain, kidneys, and the eyes. The deposits of copper cause tissue damage, death of the tissues, and scarring, which causes the affected organs to stop functioning properly.

5. Diagnosis- Wilson disease is diagnosed through a physical examination and laboratory tests. The gold standard or most ideal test is a liver biopsy

During the physical examination, a doctor will look for visible signs of Wilson disease. A special light called a slit lamp is used to look for Kayser-Fleischer rings in the eyes. Kayser-Fleischer rings are present in almost all people with Wilson disease who show signs of neurologic damage but are present in only 50 percent of those with signs of liver damage alone.

Laboratory tests measure the amount of copper in the blood, urine, and liver tissue. Most people with Wilson disease will have a lower than normal level of copper in the blood and a lower level of corresponding ceruloplasmin, a protein that carries copper in the bloodstream. In cases of acute liver failure caused by Wilson disease, the level of blood copper is often higher than normal. A 24-hour urine collection will show increased copper in the urine in most patients who display symptoms. A liver biopsy—a procedure that removes a small piece of liver tissue—can show if the liver is retaining too much copper.

Genetic testing may help diagnose Wilson disease in some people, particularly those with a family history of the disease.

Wilson disease can be misdiagnosed because it is rare and its symptoms are similar to those of other conditions.

6. Signs And Symptoms-

The disease affects mainly the following regions:

1. Liver-

A buildup of copper in the liver may cause ongoing liver disease. Chronic active hepatitis can cause cirrhosis of the liver in most patients by the time they develop symptoms. Rarely, acute liver failure occurs; most patients develop signs and symptoms that accompany chronic liver disease, including

swelling of the liver or spleen jaundice, or yellowing of the skin and whites of the eyes fluid buildup in the legs or abdomen a tendency to bruise easily fatigue

2. Central Nervous System-

A buildup of copper in the central nervous system may result in neurologic symptoms, including

problems with speech, swallowing, or physical coordination

tremors or uncontrolled movements (chorea) muscle stiffness behavioural changes twisting and repetitive movements or abnormal postures

(dystonia)

dystonia of hand due to Wilson’s disease

3. Other signs and symptoms of Wilson disease include-

anemia low platelet or white blood cell count slower blood clotting, measured by a blood test high levels of amino acids, protein, uric acid, and

carbohydrates in urine premature osteoporosis and arthritis weakening of heart muscle hypoparathyroidism (failure of the parathyroid glands,

leading to low calcium levels), infertility and habitual abortion.

4. Eyes-

Kayser-Fleischer rings result from a buildup of copper in the eyes and are the most unique sign of Wilson disease. They appear in each eye as a rusty-brown ring around the edge of the iris and in the rim of the cornea.

KAISER-FLEISCHER RING

7. Treatment-

Medical Treatment-

Wilson disease requires lifelong treatment to reduce and control the amount of copper in the body.

The drugs d-penicillamine (Cuprimine) and trientine hydrochloride (Syprine) release copper from organs into the bloodstream. Most of the copper is then filtered out by the kidneys and excreted in urine. A potential major side effect of both drugs is that neurologic symptoms can become worse. About 20% of patients experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash), myasthenia (a nerve condition leading to muscle weakness) and other drug-related effects on the kidneys and bone marrow. The risk of drug reaction and neurologic worsening appears to be lower with trientine hydrochloride.

Pregnant women should take a lower dose of d-penicillamine or trientine hydrochloride during pregnancy to reduce the risk of birth defects. A lower dose will also help reduce the risk of slower wound healing if surgical procedures are performed during childbirth.

Zinc, administered as zinc salts such as zinc acetate (Galzin), blocks the digestive tract’s absorption of copper from food. Zinc removes copper too slowly to be used alone as an initial therapy for people who already have symptoms, but it is often used in combination with d-penicillamine or trientine hydrochloride. Zinc is safe to use at full dosage during pregnancy.

In rare cases where none of the oral treatments are effective, especially in severe neurological disease, dimercaprol (British anti-Lewisite) is still occasionally necessary. This treatment is injected intramuscularly (into a muscle) every few weeks, and has a number of unpleasant side effects such as pain.

People with Wilson disease should reduce their dietary copper intake. They should not eat shellfish or liver, as these foods may contain high levels of copper. Other foods high in copper—including mushrooms, nuts, and chocolate—should be avoided. People with Wilson disease should have their drinking water checked for copper content and should not take multivitamins that contain copper.

Medication used for treating Wilson’s disease

Urine Dip Test

Liver Transplant-

Liver transplantation is the only cure for Wilson’s disease, but is used only in particular scenarios because of the numerous risks and complications associated with the procedure. It is used mainly in patients with fulminant liver failure who fail to respond to medical treatment, or in patients with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated.

Liver Transplant

9. CASE STUDYGender: Female

Age: 31

Diagnosed with Wilson’s disease at the age of 18.

Patient currently undergoing treatment at SQU Hospital, Oman.

MONTH MEDICATION PROGRESS

October, 2006

---- Clear cornea and lens.

No copper deposits in eye

March, 2009

Penicilamine,500 mgPyridoxine, 40mgHaloperidol, 2mgCalcium and Vit DZinc, 50mg

Dizziness and Unsteady gait.

Severe chorea (involuntary movement) and abdominal pain as days increase.

Less involuntary movements of face and tongue.

Liver dysfunction and cirrhosis becoming more prominent.

Signs of dysarthia (speech disorder).

Towards end of

the month, heavy bleeding observed and patient was started on mefenamic acid (500mg).

April, 2009Penicilamine,500 mgPyridoxine, 40mgHaloperidol, 2.5mgCalcium and Vit DZinc, 50mgProcyclidine, 5mg

Medication added midway:

Betahistadine, 8mg

Excessive dysarthia and chorea still observed. Improvement is noticed as month progresses.

Unsteady gait. Advised to minimise walking.

Chronic attention seeking behaviour, like faking psychiatric problems (hearing voices,etc.)

Psychiatric referral for mood swings and depression as well as suicidal tendencies.

Dentist referral due to poor dental status like tootaches, etc.

Speech is incomprehens-

ible.

Speech Therapist notes:

Patient intelligibility was low. Voice sounded hypernasal.Uses hand gestures to convey message.Patient aware that disease is affecting her voice.Therapist suggested slow speech with pauses to increase intelligibility.

Adequate mental knowledge and maturity.

Underwent oral and maxillofacial surgery – to correct injuries in hard and soft tissues of oral and maxillofacial region of face.

Patient discharged.

September,2009

Penicilamine,500 mgPyridoxine, 40mgHaloperidol, 2.5mgCalcium and Vit DZinc, 50mgProcyclidine, 5mgBetahistine, 16mg

Occasional headaches and dizziness. BP normal

Involuntary movements persisting.

Dysarthia and chorea still prominent. Eye movements

normal.

Patient discharged.

January, 2010

Penicilamine,500 mgPyridoxine, 40mgHaloperidol, 2.5mgCalcium and Vit DZinc, 50mgProcyclidine, 5mgBetahistadine, 8mg

Severe pain in both legs and inability to walk.

Slow appearance of copper deposits around the eye (Kaiser Fletscher ring).

Vitals are normal with no jaundice.

Neurological examination showed her usual choreathetotic movements in addition to impaired co-ordination. Reflexes appeared brisk.

Urine dip test appeared negative.

Patient is on regular treatment with the same medications.

She has extensive dystonia and choreoathetois. She needs rigorous neuro-rehabilitation which is not currently available in Oman.

BIBLIOGRAPHY

www.google.com www.ask.com www.wikipedia.com www.mayoclinic.com www.ninds.nih.gov