pediatrics.Wilson disease.(dr.bakr)


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pediatrics.Wilson disease.(dr.bakr)

  1. 1. Wilson Disease
  2. 2. -Wilsons disease is named after Samuel Alexander KinnierWilson (1878–1937), the British neurologist who first describedthe condition in 1912.-Wilson disease is inherited autosomal recessive disease.-A single abnormal copy of the gene is present in 1 in 100people.-The incidence is 1-4/100000-The abnormal gene for welsion disease is located on the longarm of chromosome -13-.-Because of the abnormal gene there is defect in the biliarycopper excretion , and copper incorporation into ceruloplasmin.-Wilson disease is a multisystem disorder it involvesliver,brain,eye,blood,kidney, and endocrine glandes.
  3. 3. Pathogenesis-Absence or malfunction of the gene results indecreased biliary copper excretion and diffuseaccumulation of copper in the cytosol of hepatocyte.-When liver cells become overloaded, copper isredistributed to other tissues including the brain andkidneys, to which it is toxic,primarly as a potentinhibitor of enzymatic processes.
  4. 4. Pathology-There is degenerative changes in the brain, liver andkayser-Fleischer rings in the cornea.-All grades of hepatic injury occure,there is progressiveparenchymal damage,fibrosis,and cirrhosis.-Ultrastractural changes primarily involvesmitochondria.
  5. 5. CLINICAL MANIFESTATIONWilson disease can be presents with any form of liver diseaseafter the age of -5-years,but mutation that completely knock outgene 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.
  6. 6. CLINICAL MANIFESTATIONNeurological 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 neurologicalmanifestation.- Wilsons disease is also associated with sunflower cataracts exhibitedby brown or green pigmentation of the anterior and posterior lenscapsule. Neither cause significant visual loss.
  7. 7. Psychiatric manifestation:-Depression.-Anxiety.-Psychosis.Hematological manifestation:Wilson disease may present for the first time withcoombs test negative hemolytic anemia, possiblyrelated to the release of large amount of copper fromdamaged hepatocytes.
  8. 8. Renal manifestation:Wilson disease may present with renal fanconi syndromewhich include:-Aminoaciduria.-Glycosuria.-phosphaturia.-Renal tubular acidosis.-Progressive renal failure.*Unusual manifestation include:arthritis,cardiomyopathy,endocrinopathy.
  9. 9. DIAGNOSISWilson disease should be in the differential diagnosisof 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.
  10. 10. LABORATORY INVESTIGATIONS1-Cerulopasmin:the best screening test is to measurethe serum ceruloplasmin level, most patients havedecreased cerulopasmin level,caution must be used ininterpreting ceruloplasmin level as they may beelevated in acute inflammation and in states ofelevated estrogen such as pregnancy, estrogensupplimentation,or oral contraceptive use.2-Serum copper:The serum copper level may be elevated in earlywilson disease.
  11. 11. 3-Urinary copper: urinary copper excretion is normally<40ug/day,in patient with Wilson disease is increasedto >100ug/day,and often up to 1000 ug /day or more.In equivocal cases urinary copper output in responseto chelation may be of diagnostic help.
  12. 12. 4-Liver biopsy:Liver biopsy is for diagnosis, and for determining theextent and severity of liver disease, normal coppercontent of liver is( <10ug/gm dry weight).In Wilsondisease hepatic copper content exceeds 250ug/gm dryweight.
  13. 13. 5-Genetic screening:There are more than 250 mutations in the gene have beenidentified, making diagnosis by DNA mutational analysis adifficult task unless a proband mutation is known.--Family members of patient with proven cases of Wilsonshould be screened by:-Kayser-Flescher ring.-Serum ceruloplasmin level.-Urinary copper excretion. If these result are abnormal or equivocal, liver biopsyshould be carried out.
  14. 14. TREATMENTWilson disease is progressive and fatal ,but effectivetreatment is available.1-Copper intake:Copper intake should be restricted to <1mg/day.Foods such as liver,shellfish,nuts,and chocolate shouldbe avoided.If copper content of drinking water exceed 0.1mg/L ,itmay be necessary to demineralize.
  15. 15. 2-copper chelating agent:Administration of copper chelating agent leads torapid excretion of excess deposited copper.Best chelating agent is oral D-penicillamine in dose of20mg/kg/day.Patient with neurological manifestation 10-50% ofthem when initially receive D-penicillamin have aworsening thir symptomes.
  16. 16. 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.
  17. 17. For those patient who can not tolerate D-penicillamin,other chelating agent can be use like:1-Triethylene tetramine dihydrochloride in dose of20mg/kglday.2-Ammonium tetrathiomolybdate is a new agentunder investigation for patient with neurologicalmanifestation.side effectesinclude:anemiam,lucopenia,thrombocytopenia.
  18. 18. 3-Zinc therapy:Zinc has been used as adjuvant therapy,maintenancetherapy,or primary therapy.Mecanism of action:it impair the gastrointestinalabsorbtion of copper.Dose : 25mg/8hr in children above the age of five years.4-Liver transplantation: is indicated for patient withfulminant liver failure,decompensated cirrhosis,Livertransplantation is curative with survival rate of 85-90%.
  19. 19. PROGNOSISUntreated patient with Wilson disease die ofhepatic,neurologic,renal or hematologic complication.The prognosis for patients receiving penicilamminvariable depends on time of initiation and theindividual response to chelation.In asymptomatic patient ,early initiation of chelationtherapy prevent expression of the disease.