1. Wilson Disease

2. -Wilson's disease is named after Samuel Alexander Kinnier
Wilson (1878–1937), the British neurologist who first described
the condition in 1912.
-Wilson disease is inherited autosomal recessive disease.
-A single abnormal copy of the gene is present in 1 in 100
people.
-The incidence is 1-4/100000
-The abnormal gene for welsion disease is located on the long
arm of chromosome -13-.
-Because of the abnormal gene there is defect in the biliary
copper excretion , and copper incorporation into ceruloplasmin.
-Wilson disease is a multisystem disorder it involves
liver,brain,eye,blood,kidney, and endocrine glandes.

4. Pathogenesis
-Absence or malfunction of the gene results in
decreased biliary copper excretion and diffuse
accumulation of copper in the cytosol of hepatocyte.
-When liver cells become overloaded, copper is
redistributed to other tissues including the brain and
kidneys, to which it is toxic,primarly as a potent
inhibitor of enzymatic processes.

5. Pathology
-There is degenerative changes in the brain, liver and
kayser-Fleischer rings in the cornea.
-All grades of hepatic injury occure,there is progressive
parenchymal damage,fibrosis,and cirrhosis.
-Ultrastractural changes primarily involves
mitochondria.

8. CLINICAL MANIFESTATION
Wilson disease can be presents with any form of liver disease
after the age of -5-years,but mutation that completely knock out
gene function are associated with disease onset as early as ( 2-
3)years of age.
Wilsonian hepatic disease include:
-Asymptomatic hepatomegaly with or without splenomegaly.
-Sub acute or chronic hepatitis.
-Fulminant hepatic failure, three times more common in female
-Liver cirrhosis with portal hypertention,ascites
edema,varecial bleeding.
-Other effects of hepatic dysfunction like:
delayed puberty,amenorrhea,coagulation defect.

9. CLINICAL MANIFESTATION
Neurological manifestations:
After-20-years of age, neurologic symptoms predominate.
Neurologic disorders may present with:
-Intention tremor.
-Dysarthria.
-Dystonia.
-Lack of motor coordination.
-Deterioration in school performance.
-Behavior changes.
-Kayser-Fleischer ring always present in patient with neurological
manifestation.
- Wilson's disease is also associated with sunflower cataracts exhibited
by brown or green pigmentation of the anterior and posterior lens
capsule. Neither cause significant visual loss.

10. Psychiatric manifestation:
-Depression.
-Anxiety.
-Psychosis.
Hematological manifestation:
Wilson disease may present for the first time with
coombs test negative hemolytic anemia, possibly
related to the release of large amount of copper from
damaged hepatocytes.

11. Renal manifestation:
Wilson disease may present with renal fanconi syndrome
which include:
-Aminoaciduria.
-Glycosuria.
-phosphaturia.
-Renal tubular acidosis.
-Progressive renal failure.
*Unusual manifestation include:
arthritis,cardiomyopathy,endocrinopathy.

12. DIAGNOSIS
Wilson disease should be in the differential diagnosis
of children or teenager presenting with:
1-Unexplained acute or chronic liver disease.
2-Neurologic symptoms of unknown cause.
3-Acute hemolysis.
4-Psychiatric illness.
5-Behaiveral changes.
6-Fanconi syndrome.

13. LABORATORY INVESTIGATIONS
1-Cerulopasmin:the best screening test is to measure
the serum ceruloplasmin level, most patients have
decreased cerulopasmin level,caution must be used in
interpreting ceruloplasmin level as they may be
elevated in acute inflammation and in states of
elevated estrogen such as pregnancy, estrogen
supplimentation,or oral contraceptive use.
2-Serum copper:
The serum copper level may be elevated in early
wilson disease.

14. 3-Urinary copper: urinary copper excretion is normally
<40ug/day,in patient with Wilson disease is increased
to >100ug/day,and often up to 1000 ug /day or more.
In equivocal cases urinary copper output in response
to chelation may be of diagnostic help.

15. 4-Liver biopsy:
Liver biopsy is for diagnosis, and for determining the
extent and severity of liver disease, normal copper
content of liver is( <10ug/gm dry weight).In Wilson
disease hepatic copper content exceeds 250ug/gm dry
weight.

16. 5-Genetic screening:
There are more than 250 mutations in the gene have been
identified, making diagnosis by DNA mutational analysis a
difficult task unless a proband mutation is known.
--Family members of patient with proven cases of Wilson
should be screened by:
-Kayser-Flescher ring.
-Serum ceruloplasmin level.
-Urinary copper excretion.
If these result are abnormal or equivocal, liver biopsy
should be carried out.

17. TREATMENT
Wilson disease is progressive and fatal ,but effective
treatment is available.
1-Copper intake:
Copper intake should be restricted to <1mg/day.
Foods such as liver,shellfish,nuts,and chocolate should
be avoided.
If copper content of drinking water exceed 0.1mg/L ,it
may be necessary to demineralize.

18. 2-copper chelating agent:
Administration of copper chelating agent leads to
rapid excretion of excess deposited copper.
Best chelating agent is oral D-penicillamine in dose of
20mg/kg/day.
Patient with neurological manifestation 10-50% of
them when initially receive D-penicillamin have a
worsening thir symptomes.

19. Side effects of D-penicillamin include:
1-Goodpature syndrome.
2-Systemic lupus erythematosis.
3-Polymyositis.
4-Aplastic anemia.
5-Nephrosis.
6-Deficiency of other elements like zinc.
7-Vitamin B6 deficiency.

20. For those patient who can not tolerate D-
penicillamin,other chelating agent can be use like:
1-Triethylene tetramine dihydrochloride in dose of
20mg/kglday.
2-Ammonium tetrathiomolybdate is a new agent
under investigation for patient with neurological
manifestation.side effectes
include:anemiam,lucopenia,thrombocytopenia.

21. 3-Zinc therapy:
Zinc has been used as adjuvant therapy,maintenance
therapy,or primary therapy.
Mecanism of action:it impair the gastrointestinal
absorbtion of copper.
Dose : 25mg/8hr in children above the age of five years.
4-Liver transplantation: is indicated for patient with
fulminant liver failure,decompensated cirrhosis,Liver
transplantation is curative with survival rate of 85-90%.

22. PROGNOSIS
Untreated patient with Wilson disease die of
hepatic,neurologic,renal or hematologic complication.
The prognosis for patients receiving penicilammin
variable depends on time of initiation and the
individual response to chelation.
In asymptomatic patient ,early initiation of chelation
therapy prevent expression of the disease.