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.

WILSON DISEASE & GENERAL DISCUSSION ON COPPER METABOLISM.

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    Wilson disease & general discussion on copper metabolism Wilson disease & general discussion on copper metabolism Presentation Transcript

    • 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(Normal & Abnormal) Wilson Disease – Pathophysiology Clinical Features Laboratory Diagnosis Treatment Prevention References
    • WILSON DISEASEProgressive lenticular degenerationA familial nervous disease associated with cirrhosis of liver SAK Wilson 1911
    • 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 metalloenzymesMost copper in plasma is bound to caeruloplasmin
    • 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
    • COPPER METABOLISM
    • Wilson disease genetic linkAutosomal recessive disorderWD gene ATP7B encodes a copper transporting P-Type ATPase which is expressed predominantly in liver
    • Molecular mechanismWD protein (WNDP) has 2 functions :Export of copper from cellIncorporation into copper dependent enzymes
    • 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 histidine to a glutamine
    • 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.
    • Clinical featuresClinical presentation is extremely variable :
    • 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
    •  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 Wilson Disease KF ring may be found in chronic liver disease- familial cholestatic syndromes
    • Laboratory diagnosisPresence of KAYSER FLEISHER RINGCaeruloplasmin level < 20mg/dayUrinary copper excretion rate > 100mg/day
    • Hepatic copper concentration : Liver Biopsy with sufficient tissue reveals levels of > 250mg/g of dry weight
    • Imaging studies CT & MRI of brain and abdomen can be carried out to confirm diagnosis
    • Imaging studies KAYSER FLEISHER RING diagnosed definitively by OPHTHALMOLOGIST using SLIT LAMP
    • 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
    • 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 : gastritis, aplastic anaemia
    • 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
    • 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 kinky hair disease
    • referencesDr.Namrata Blog – Biochemistry for MedicsClass notesInternet
    • Thank you