Wilson`s disease

This presentation is made summarizing different textbook.

1. WELOMCE

2. Wilson`s Disease Dr. Md. Rafiqul Islam Registrar(Medicine) Medicine Unit-1 M Abdur Rahim Medical College Hospital Dinajpur .

3. Wilson`s Disease -Autosomal recessive, rare -Total body copper increased with excess copper deposition in,and damaging to several organs -Clinical manifestations are caused by copper toxicity and primarily involve the liver and the brain

4. Pathophysiology Normally dietary copper absorbed from the stomach and proximal small intestine Then rapidly taken into the liver In the liver it is stored and incorporated into ceruloplasmin It then secreted in into the blood ATP7B protein deficiency impairs biliary copper excretion, resulting in positive copper balance, hepatic copper accumulation, and copper toxicity from oxidant damage

5. Pathophysiology contd. In Wilsons disease almost always failure of synthesis of ceruloplasmin The amount of copper at birth is normal Thereafter it increases steadily The organs most affected are liver,basal ganglia of brain,eyes,kidneys and skeleton

6. Clinical Features Symptoms usually arise between ages 15-45 years Hepatic disease occurs predominantly in childhood and adolescence(can be present at fifties also),Neuropsychiatric disorders in Adults. Neurological feature:Basal ganglia syndrome and dementia(late adolescence) These feature can occur alone or simultaneously Others:renal tubular damage and osteoporosis(rare)

7. Clinical Features contd. Liver disease: - Episodes of acute hepatitis can occur(with or without jaundice). - Chronic hepatitis can develop insidiously and eventually present with established cirrhosis. - Liver failure and portal hypertension may supervene. - In Severe hepatic failure, hemolytic anemia may develop because large amounts of copper derived from hepatocellular necrosis are released into the bloodstream. Association of hemolysis and liver disease makes Wilson’s disease a likely diagnosis

8. Clinical Features contd. Neurological feature: Typically occur in patients in their early twenties, although the age of onset extends into the sixth decade of life Tremor,choreoathetosis,dystonia and dementia Unusual clumsiness for age; Patients have difficulty focusing on tasks, but cognition usually is not grossly impaired Autonomic disturbances may include orthostatic hypotension and sweating abnormalities as well as bowel, bladder, and sexual dysfunction Neurological disease typically develops after the onset of liver disease and can be prevented by effective treatment following diagnosis of liver disease phase

9. Kayser-Fleischer ring: It is characterised by greenish -brown discoloration of the corneal margin appearing first at the upper periphery Single clinical clue to diagnosis Can be seen in 60% adults with Wilsons disease Disappear with treatment Usually present with neuropsychiatric disease,may be absent in hepatic disease

10. Kayser-Fleischer ring

11. Investigations Low serum ceruloplasmin is single most laboratory clue to diagnosis Oter features of disordered copper metabolism should be sought such as a)High free serum copper b)High urine copper excretion of greater than 0.6 micromole/24hrs (38microgram/24 hrs ) and a very high hepatic content Measuring 24-hour urinary copper excretion giving D-penicillamine is a useful confirmatory test (more than 25 micromole/ 24 hrs is considered Diagnostic

12. Lipzig Criteria

13. Management The first step in evaluating patients presenting with hepatic decompensation is to establish disease severity, which can be estimated with the Nazer prognostic index Score <7: medical therapy Score >9:should be considered immediately for liver transplantation Score >7 & <9:clinical judgment is required in deciding whether to recommend transplantation or medical therapy

14. Penicillamine (copper binding agent) is drug of choice Dose range 1-4 g The dose must be sufficient to produce cupriuresis and most patient require 1.5g/day Pyridoxin should be added Dose should be reduced once the disease in remission Treatment should be continued lifelong even in pregnancy Abrupt discontinuation of treatment must be avoided because this may precipitate acute liver failure.

15. Side effect of penicillamine Occur in one third of patients Includes rashes,protein loosing nephropathy,lupus -like syndrome and bone marrow depression If these occur then trientine dihydrochloride (1.2-2.4 g/day) and zinc (50 mg 3 times daily) are potential alternatives

16. Liver transplantation is indicated for fulminant liver failure or advanced cirrhosis with liver failure

17. MONITORING ANTICOPPER THERAPY When trientine or penicillamine is first used, it is necessary to monitor for drug toxicity, particularly bone marrow suppression and proteinuria. The anticopper effects of trientine and penicillamine can be monitored by following 24-h “free” serum copper levels Complete blood counts, standard biochemical profiles, and a urinalysis should be performed at -weekly intervals for 1 month, then -twice-weekly intervals for 2 or 3 months, then -monthly intervals for 3 or 4 months, and -at 4- to 6-month intervals thereafter. Zinc treatment does not require monitoring of blood or urine for toxicity.

18. Prognosis is excellent, provided treatment is started before there is irreversible damage. With treatment, liver function usually recovers after about a year although residual liver damage is usually present. Neurologic and psychiatric symptoms usually improve after 6–24 months of treatment. Siblings and children of patients with Wilson’s disease must be investigated and treatment should be given to all affected individuals, even if they are asymptomatic. Siblings of a diagnosed patient have a 1 in 4 risk of Wilson’s disease, whereas children of an affected patient have about a 1 in 200 risk

19. Thank You