Biochemistry for Medicswww.namrata.co
NAME : PURANG VASHISHROLL NUMBER : 68 (NEW-70)
TABLE OF CONTENTS Wilson Disease - Epidemology Copper Metabolism Wilson Disease – Genetic Link Molecular Metabolism(No...
WILSON DISEASEProgressive lenticular degenerationA familial nervous disease associated with cirrhosis of liver          ...
EPIDEMOLOGYOccurs worldwideIncidence of 1 in 30000Age of onset of symptoms ranges from 6 to 40 yrs
Overview of copper metabolismCopper is an essential trace element which is a component of many intracellular metalloenzym...
Copper metabolism 50% daily dietary Cu absorbed from stomach & small  intestine Absorbed Cu transported to liver in port...
COPPER METABOLISM
Wilson disease genetic linkAutosomal recessive disorderWD gene ATP7B encodes a copper transporting P-Type ATPase which i...
Molecular mechanismWD protein (WNDP) has 2 functions :Export of copper from cellIncorporation into copper dependent enzy...
NORMAL COPPER METABOLISM
ABNORMAL COPPER METABOLISM
MUTATIONS IN WD GENEDeletions – 60Nonsense – 19Insertions – 21Missense – 166Splice – 23Most common is change fromA h...
WD PATHOPHYSIOLOGYMutations in gene result in :Retention of Cu in liverImpaired incorporation of Cu in CaeruloplasminThi...
Clinical featuresClinical presentation is extremely variable :
HEPATIC PRESENTATIONMore common in children than in adultsSymptoms may be vague & non specificPatients present with hep...
 Hepatic decompensation associated with :ASCITES
Peripheral OedemaHepatic Encephalopathy
neurological presentationTends to occur in 2nd & 3rd decades or later3 main movements disorders :      DYSTONIA
TREMOR         AND INCOORDINATION
PSYCHIATRIC PRESENTATON20% of patients present with purely psychiatric symptomsFeatures are :Loss of emotionalcontrol
Aggressive & Anti-social behaviours
Occular signsClassic KAYSERFLEISHER RINGcaused by Cu depositionin Descemet’smembrane
SUNFLOWERCATARACTS due to Cudeposition in the lens
% of cases having kayser fleisher ringHepaticinvolvement – 30-50%Neurologicinvolvement – 95% KF rings not  specific for  ...
Laboratory diagnosisPresence of KAYSER FLEISHER RINGCaeruloplasmin level < 20mg/dayUrinary copper excretion rate > 100m...
Hepatic copper concentration :                          Liver Biopsy with                          sufficient tissue reve...
Imaging studies         CT & MRI of brain and         abdomen can be carried         out to confirm diagnosis
Imaging studies           KAYSER FLEISHER           RING diagnosed           definitively by           OPHTHALMOLOGIST    ...
treatmentD Penicillamine(previously used because toxic)-mode : general chelator        : induces urinary Cu excretion-dos...
D-penicillamine-side effects : fever,rash,aplastic anaemialeukopenia,nephrotic syndrome,thrombocytopenia
TRIENTINELess toxicMode : general chelator         : induces urinary copper excretionDose : 1-1.2g/daySide effects : g...
zincFor patients with hepatitis/cirrhosis but without evidence of neurologic symptomsMode : blocks intestinal absorption...
B6 & dimercaprolUsed as part of treatment
Evolution of Wilson disease
prevention      GENETIC      COUNSELLING      recommended for people with      family history of Wilson’s      Disease
OTHER COPPER DISEASES1. Idiopathic Copper Toxicosis2. Tyrolian Infantile Cirrhosis3. Indian Childhood Cirrhosis4. Menk’s k...
referencesDr.Namrata Blog – Biochemistry for MedicsClass notesInternet
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Wilson disease & general discussion on copper metabolism

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WILSON DISEASE & GENERAL DISCUSSION ON COPPER METABOLISM.

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Wilson disease & general discussion on copper metabolism

  1. 1. Biochemistry for Medicswww.namrata.co
  2. 2. NAME : PURANG VASHISHROLL NUMBER : 68 (NEW-70)
  3. 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. 4. WILSON DISEASEProgressive lenticular degenerationA familial nervous disease associated with cirrhosis of liver SAK Wilson 1911
  5. 5. EPIDEMOLOGYOccurs worldwideIncidence of 1 in 30000Age of onset of symptoms ranges from 6 to 40 yrs
  6. 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. 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. 8. COPPER METABOLISM
  9. 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. 10. Molecular mechanismWD protein (WNDP) has 2 functions :Export of copper from cellIncorporation into copper dependent enzymes
  11. 11. NORMAL COPPER METABOLISM
  12. 12. ABNORMAL COPPER METABOLISM
  13. 13. MUTATIONS IN WD GENEDeletions – 60Nonsense – 19Insertions – 21Missense – 166Splice – 23Most common is change fromA histidine to a glutamine
  14. 14. WD PATHOPHYSIOLOGYMutations in gene result in :Retention of Cu in liverImpaired incorporation of Cu in CaeruloplasminThis accumulation is followed byHepatic & neurological symptomsDue to copper toxicity.
  15. 15. Clinical featuresClinical presentation is extremely variable :
  16. 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. 17.  Hepatic decompensation associated with :ASCITES
  18. 18. Peripheral OedemaHepatic Encephalopathy
  19. 19. neurological presentationTends to occur in 2nd & 3rd decades or later3 main movements disorders : DYSTONIA
  20. 20. TREMOR AND INCOORDINATION
  21. 21. PSYCHIATRIC PRESENTATON20% of patients present with purely psychiatric symptomsFeatures are :Loss of emotionalcontrol
  22. 22. Aggressive & Anti-social behaviours
  23. 23. Occular signsClassic KAYSERFLEISHER RINGcaused by Cu depositionin Descemet’smembrane
  24. 24. SUNFLOWERCATARACTS due to Cudeposition in the lens
  25. 25. % of cases having kayser fleisher ringHepaticinvolvement – 30-50%Neurologicinvolvement – 95% KF rings not specific for Wilson Disease KF ring may be found in chronic liver disease- familial cholestatic syndromes
  26. 26. Laboratory diagnosisPresence of KAYSER FLEISHER RINGCaeruloplasmin level < 20mg/dayUrinary copper excretion rate > 100mg/day
  27. 27. Hepatic copper concentration : Liver Biopsy with sufficient tissue reveals levels of > 250mg/g of dry weight
  28. 28. Imaging studies CT & MRI of brain and abdomen can be carried out to confirm diagnosis
  29. 29. Imaging studies KAYSER FLEISHER RING diagnosed definitively by OPHTHALMOLOGIST using SLIT LAMP
  30. 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. 31. D-penicillamine-side effects : fever,rash,aplastic anaemialeukopenia,nephrotic syndrome,thrombocytopenia
  32. 32. TRIENTINELess toxicMode : general chelator : induces urinary copper excretionDose : 1-1.2g/daySide effects : gastritis, aplastic anaemia
  33. 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. 34. B6 & dimercaprolUsed as part of treatment
  35. 35. Evolution of Wilson disease
  36. 36. prevention GENETIC COUNSELLING recommended for people with family history of Wilson’s Disease
  37. 37. OTHER COPPER DISEASES1. Idiopathic Copper Toxicosis2. Tyrolian Infantile Cirrhosis3. Indian Childhood Cirrhosis4. Menk’s kinky hair disease
  38. 38. referencesDr.Namrata Blog – Biochemistry for MedicsClass notesInternet
  39. 39. Thank you
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