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WILSON DISEASE & GENERAL DISCUSSION ON

COPPER METABOLISM

NAME : PURANG VASHISH

ROLL NUMBER : 68 (NEW-70)

TABLE OF CONTENTSWilson Disease - EpidemologyCopper MetabolismWilson Disease – Genetic LinkMolecular Metabolism(Normal & Abnormal) Wilson Disease – PathophysiologyClinical FeaturesLaboratory DiagnosisTreatmentPreventionReferences

WILSON DISEASEProgressive lenticular degenerationA familial nervous disease associated with

cirrhosis of liver

SAK Wilson1911

EPIDEMOLOGYOccurs worldwide

Incidence of 1 in 30000

Age of onset of symptoms ranges from 6 to 40 yrs

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

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

COPPER METABOLISM

Wilson disease genetic linkAutosomal 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 GENEDeletions – 60Nonsense – 19Insertions – 21Missense – 166Splice – 23Most common is change fromA histidine to a glutamine

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.

Clinical featuresClinical presentation is extremely variable :

HEPATIC PRESENTATIONMore common in children than in adultsSymptoms may be vague & non specificPatients present with hepatitis , cirrhosisWD may manifest as severe hepatic failure

Hepatic decompensation associated with :

ASCITES

Peripheral Oedema

Hepatic Encephalopathy

neurological presentationTends to occur in 2nd & 3rd decades or later3 main movements disorders :

DYSTONIA

TREMOR

AND INCOORDINATION

PSYCHIATRIC PRESENTATON20% of patients present with purely

psychiatric symptomsFeatures are :

Loss of emotional control

Aggressive & Anti-social behaviours

Occular signs

Classic KAYSER FLEISHER RING caused by Cu deposition in Descemet’s membrane

SUNFLOWER CATARACTS due to Cu deposition in the lens

% 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

Laboratory diagnosisPresence 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

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

D-penicillamine-side effects : fever,rash,aplastic anaemia leukopenia,nephrotic syndrome,thrombocytopenia

TRIENTINELess toxicMode : general chelator : induces urinary copper excretionDose : 1-1.2g/daySide effects : gastritis, aplastic anaemia

zincFor patients with hepatitis/cirrhosis but

without evidence of neurologic symptomsMode : blocks intestinal absorption of copperDose : 50mgSide effects : gastritis, zinc accumulation,

changes in immune

B6 & dimercaprolUsed 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

referencesDr.Namrata Blog – Biochemistry for MedicsClass notesInternet

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