Wilson disease & general discussion on copper metabolism
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Transcript of Wilson disease & general discussion on copper metabolism
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Selected for publication in student’s corner
Biochemistry for Medicswww.namrata.co
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WILSON DISEASE & GENERAL DISCUSSION ON
COPPER METABOLISM
NAME : PURANG VASHISH
ROLL NUMBER : 68 (NEW-70)
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TABLE OF CONTENTSWilson Disease - EpidemologyCopper MetabolismWilson Disease – Genetic LinkMolecular Metabolism(Normal & Abnormal) Wilson Disease – PathophysiologyClinical FeaturesLaboratory DiagnosisTreatmentPreventionReferences
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WILSON DISEASEProgressive lenticular degenerationA familial nervous disease associated with
cirrhosis of liver
SAK Wilson1911
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EPIDEMOLOGYOccurs worldwide
Incidence of 1 in 30000
Age of onset of symptoms ranges from 6 to 40 yrs
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Overview of copper metabolismCopper is an essential trace element which is
a component of many intracellular metalloenzymes
Most copper in plasma is bound to caeruloplasmin
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Copper metabolism50% daily dietary Cu absorbed from stomach &
small intestineAbsorbed Cu transported to liver in portal blood
bound to albuminThen exported to peripheral tissues mainly bound
to caeruloplasmin & lesser extent to albuminHighest concentration of Cu in liver and kidneySignificant amount in cardiac muscle , skeletal
muscle & bonesExcess excreted in bile & then in to gut
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COPPER METABOLISM
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Wilson disease genetic linkAutosomal recessive disorder
WD gene ATP7B encodes a copper transporting P-Type ATPase which is expressed predominantly in liver
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Molecular mechanismWD protein (WNDP) has 2 functions :
Export of copper from cell
Incorporation into copper dependent enzymes
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NORMAL COPPER METABOLISM
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ABNORMAL COPPER METABOLISM
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MUTATIONS IN WD GENEDeletions – 60Nonsense – 19Insertions – 21Missense – 166Splice – 23Most common is change fromA histidine to a glutamine
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WD PATHOPHYSIOLOGYMutations in gene result in : Retention of Cu in liverImpaired incorporation of Cu in
Caeruloplasmin
This accumulation is followed byHepatic & neurological symptomsDue to copper toxicity.
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Clinical featuresClinical presentation is extremely variable :
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HEPATIC PRESENTATIONMore common in children than in adultsSymptoms may be vague & non specificPatients present with hepatitis , cirrhosisWD may manifest as severe hepatic failure
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Hepatic decompensation associated with :
ASCITES
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Peripheral Oedema
Hepatic Encephalopathy
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neurological presentationTends to occur in 2nd & 3rd decades or later3 main movements disorders :
DYSTONIA
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TREMOR
AND INCOORDINATION
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PSYCHIATRIC PRESENTATON20% of patients present with purely
psychiatric symptomsFeatures are :
Loss of emotional control
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Aggressive & Anti-social behaviours
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Occular signs
Classic KAYSER FLEISHER RING caused by Cu deposition in Descemet’s membrane
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SUNFLOWER CATARACTS due to Cu deposition in the lens
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% of cases having kayser fleisher ring
Hepatic involvement – 30-50%Neurologic involvement – 95% KF rings not
specific for Wilson Disease
KF ring may be found in chronic liver disease-familial cholestatic syndromes
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Laboratory diagnosisPresence of KAYSER FLEISHER RING
Caeruloplasmin level < 20mg/day
Urinary copper excretion rate > 100mg/day
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Hepatic copper concentration :
Liver Biopsy with sufficient tissue reveals levels of > 250mg/g of dry weight
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Imaging studies
CT & MRI of brain and abdomen can be carried out to confirm diagnosis
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Imaging studies
KAYSER FLEISHER RING diagnosed definitively by OPHTHALMOLOGIST using SLIT LAMP
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treatmentD 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
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D-penicillamine-side effects : fever,rash,aplastic anaemia leukopenia,nephrotic syndrome,thrombocytopenia
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TRIENTINELess toxicMode : general chelator : induces urinary copper excretionDose : 1-1.2g/daySide effects : gastritis, aplastic anaemia
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zincFor patients with hepatitis/cirrhosis but
without evidence of neurologic symptomsMode : blocks intestinal absorption of copperDose : 50mgSide effects : gastritis, zinc accumulation,
changes in immune
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B6 & dimercaprolUsed as part of treatment
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Evolution of Wilson disease
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prevention
GENETIC COUNSELLING recommended for people with family history of Wilson’s Disease
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OTHER COPPER DISEASES1. Idiopathic Copper Toxicosis2. Tyrolian Infantile Cirrhosis3. Indian Childhood Cirrhosis4. Menk’s kinky hair disease
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referencesDr.Namrata Blog – Biochemistry for MedicsClass notesInternet
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Thank you