Copper Overload: Understanding Wilson Disease and Its Impact on Health”
When to suspect?
Female > male Children/teenagers with unexplained acute or chronic liver disease with/without neurologic symptoms of unkown cause , acute hemolysis (coombs negative)’ Psychiatric illness, behavioral changes, Fanconi syndrome or unexplained bone or muscle disease
Investigation for wilson disease
1-Decreased Serum ceruloplasmin (<20mg/dl)
High:acute inflammation ,high estrogen states like pregnancy ,estrogen supplementation ,ocp
Low: – Autoimmune hepatitis ,Celiac ds; familial aceruloplasminemia
2-Serum-free copper (> 1.6μmol/L)
3-Urinary copper excretion > 100 ug/day suggestive of WD (usually normally <40 ug/day)
D-penicillamine challenge
4-KF RING in slit lamp examination
50% With hepatic disease and 95% with neuro symptom
5-Liver biopsy (Measuring hepatic copper Content
[Normally < 10micro gm /gm dry weight)
Wilson > 250 μg/g dry weight (>4 micromol/gm dry wt)
6-Genetic screening-Linkage analysis or direct DNA mutation analysis(H1069Q& mutation)
TREATMENT OF WILSON DISEASE
1-Dietary restriction (Cu intake < 1 mg /day)
[food to be avoided liver, shellfish, nuts, chocolate
2-Copper chelating agent
Initial therapy in symptomatic patients –
To reduce copper to a Subtoxic level Which usually takes 6 months
– D-penicillamine (β, β-dimethyl cysteine)
MOA-Induction of metallothionein in the Liver favoring lysosomal seq..
– Trientene (2nd Line)
– Zinc ( Slow in action)
–Ammonium tetrathiomolybdate
Maintenance therapy
Aim to maintain negative copper balance so as to prevent copper accumulation & toxicity
D- penicillamine
Trientine
Zinc
3-Antioxidants (Vit E, Curcumin) and pharmacologic chaperones (4-phenylbutyrate A Curcumin)
4- Liver transplantation
Screening of family members of patients with proven case
Test include serum ceruloplasmin and urinary copper excretion .Liver biopsy in case of abnormal or equivocal results