Updated management of Wilson's disease

A classroom presentation

1. Presented by Dr. Sainy Azeez Intern Doctor Updated Management of Wilson’s Disease

2. Introduction Inborn error of Cu metabolism. Autosomal recessive inheritance. Hepatolenticular degeneration. Cu deposition in Liver Basal ganglia of brain Cornea Kidney Skeleton

3. Incidence 1 in 30,000 to 1 in 1,00,000

4. Etiology Molecular defect within a gene (ATP7B) on chromosome 13.

5. Pathophysiology Dietary Cu absorbed from stomach & upper SI Liver Stored & incorporated into Bile Caeruloplasmin Faeces Blood

6. Clinical Features Age: 5-40 years Children & young adults: Hepatic problems Older adults : Neurological problems.

7. Hepatic Symptoms Acute Hepatitis Acute fulminant liver failure Chronic Hepatitis Cirrhosis Portal HTN Liver failure

8. Neurological Symptoms Tremor Choreoathetosis Dysarthria Dystonia Parkinsonism Dementia

9. Eye: Kayser Fleischer ring Kidney: Renal tubular damage Bone: Osteoporosis

10. Investigations Serum Caeruloplasmin : low or normal 24hours urinary Cu excretion:> 0.6 μ mol/24hrs Free serum Cu conc. : High >25 μ gm/dl Liver biopsy: Hepatic Cu content >250 μ gm/gm 24hours urinary Cu excretion while giving D- penicillamine : >25 μ mol/24hrs Genetic testing

11. Management Counselling of the patient Diet: Avoidence of food rich in Cu Drug therapy: D- Penicillamine Trientine Zinc Tetrathiomolybdate

12. D- Penicillamine Mode of action: Cu binding agent & induces cupruria . Dose: 1-1.5gm in 2-4 divided doses daily. Side effects: Skin rash Protein losing nephropathy Lupus like syndrome Bone marrow depression Serous retinitis . May aggrevate neurological symptoms.

13. Trientine Mode of action : Cu binding agent & induces cupruria . Dose: 1.2-1.8gm/day Side effects: Gastritis Aplastic anaemia

14. Zinc Acetate Mode of action: Blocks intestinal absorption of Cu. Dose: 50mg 8 hourly. Side effects: Gastritis Biochemical Pancratitis

15. Tetrathiomolybdate Mode of action: Cu binding agent & blocks intestinal absorption of Cu. Side effects: Bone marrow depression Hepatotoxicity .

16. Liver Transplantation Fulminant hepatic failure or decompensated cirrhosis.

17. Treatment during pregnancy Drugs should be continued. Doses of D- Penicillamine & Trientine should be reduced by 25%

18. Prognosis Prognosis is excellent when treatment started before irreversible damage. Without treatment death may occur.

19. Thank You THANK YOU