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
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
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
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.
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
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
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