This document provides an overview of Wilson disease, including its epidemiology, genetics, pathophysiology, clinical features, diagnosis, and treatment. Key points include: - Wilson disease is an autosomal recessive disorder caused by mutations in the ATP7B gene resulting in copper accumulation. - It occurs worldwide with an incidence of 1 in 30,000. Symptoms typically onset between ages 6-40. - Clinical presentation can include hepatic, neurological, and psychiatric features. Kayser-Fleischer rings seen on eye exam and low ceruloplasmin levels support diagnosis. - Treatment involves chelation therapy with penicillamine or trientine to remove excess copper from the body. Zinc can also

1. Biochemistry for Medics
www.namrata.co

2. NAME : PURANG VASHISH
ROLL NUMBER : 68 (NEW-70)

3. TABLE OF CONTENTS
 Wilson Disease - Epidemology
 Copper Metabolism
 Wilson Disease – Genetic Link
 Molecular Metabolism(Normal & Abnormal)
 Wilson Disease – Pathophysiology
 Clinical Features
 Laboratory Diagnosis
 Treatment
 Prevention
 References

4. WILSON DISEASE
Progressive lenticular degeneration
A familial nervous disease associated with cirrhosis
of liver
SAK Wilson
1911

5. EPIDEMOLOGY
Occurs worldwide
Incidence of 1 in 30000
Age of onset of symptoms ranges from 6 to 40 yrs

6. Overview of copper metabolism
Copper is an essential trace element which is a
component of many intracellular metalloenzymes
Most copper in plasma is bound to caeruloplasmin

7. Copper metabolism
 50% daily dietary Cu absorbed from stomach & small
intestine
 Absorbed Cu transported to liver in portal blood bound to
albumin
 Then exported to peripheral tissues mainly bound to
caeruloplasmin & lesser extent to albumin
 Highest concentration of Cu in liver and kidney
 Significant amount in cardiac muscle , skeletal muscle &
bones
 Excess excreted in bile & then in to gut

8. COPPER METABOLISM

9. Wilson disease genetic link
Autosomal recessive disorder
WD gene ATP7B encodes a copper transporting
P-Type ATPase which is expressed
predominantly in liver

10. Molecular mechanism
WD protein (WNDP) has 2 functions :
Export of copper from cell
Incorporation into copper dependent enzymes

11. NORMAL COPPER METABOLISM

12. ABNORMAL COPPER METABOLISM

13. MUTATIONS IN WD GENE
Deletions – 60
Nonsense – 19
Insertions – 21
Missense – 166
Splice – 23
Most common is change from
A histidine to a glutamine

14. WD PATHOPHYSIOLOGY
Mutations in gene result in :
Retention of Cu in liver
Impaired incorporation of Cu in Caeruloplasmin
This accumulation is followed by
Hepatic & neurological symptoms
Due to copper toxicity.

15. Clinical features
Clinical presentation is extremely variable :

16. HEPATIC PRESENTATION
More common in children than in adults
Symptoms may be vague & non specific
Patients present with hepatitis , cirrhosis
WD may manifest as severe hepatic failure

17.  Hepatic decompensation associated with :
ASCITES

18. Peripheral Oedema
Hepatic Encephalopathy

19. neurological presentation
Tends to occur in 2nd & 3rd decades or later
3 main movements disorders :
DYSTONIA

20. TREMOR
AND INCOORDINATION

21. PSYCHIATRIC PRESENTATON
20% of patients present with purely psychiatric
symptoms
Features are :
Loss of emotional
control

22. Aggressive & Anti-
social behaviours

23. Occular signs
Classic KAYSER
FLEISHER RING
caused by Cu deposition
in Descemet’s
membrane

24. SUNFLOWER
CATARACTS due to Cu
deposition in the lens

25. % of cases having kayser fleisher ring
Hepatic
involvement – 30-
50%
Neurologic
involvement – 95%
 KF rings not
specific for
Wilson Disease
 KF ring may be
found in chronic
liver disease-
familial
cholestatic
syndromes

26. Laboratory diagnosis
Presence of KAYSER FLEISHER RING
Caeruloplasmin level < 20mg/day
Urinary copper excretion rate > 100mg/day

27. Hepatic copper concentration :
Liver Biopsy with
sufficient tissue reveals
levels of > 250mg/g of dry
weight

28. Imaging studies
CT & MRI of brain and
abdomen can be carried
out to confirm diagnosis

29. Imaging studies
KAYSER FLEISHER
RING diagnosed
definitively by
OPHTHALMOLOGIST
using SLIT LAMP

30. treatment
D Penicillamine(previously used because toxic)
-mode : general chelator
: induces urinary Cu excretion
-dose initial : 1-1.5g/day for adults
: 20mg/kg/day for children

31. D-penicillamine
-side effects : fever,rash,aplastic anaemia
leukopenia,nephrotic syndrome,thrombocytopenia

32. TRIENTINE
Less toxic
Mode : general chelator
: induces urinary copper excretion
Dose : 1-1.2g/day
Side effects : gastritis, aplastic anaemia

33. zinc
For patients with hepatitis/cirrhosis but without
evidence of neurologic symptoms
Mode : blocks intestinal absorption of copper
Dose : 50mg
Side effects : gastritis, zinc accumulation, changes in
immune

34. B6 & dimercaprol
Used as part of treatment

35. Evolution of Wilson disease

36. prevention
GENETIC
COUNSELLING
recommended for people with
family history of Wilson’s
Disease

37. OTHER COPPER DISEASES
1. Idiopathic Copper Toxicosis
2. Tyrolian Infantile Cirrhosis
3. Indian Childhood Cirrhosis
4. Menk’s kinky hair disease

38. references
Dr.Namrata Blog – Biochemistry for Medics
Class notes
Internet

39. Thank you