Wilson’s Disease

Dr. Imtiyaz Hashim

PGR MU-IV(B)
 What is Wilson’s Disease?
Autosomal recessive disorder that prevents the body from getting rid of extra
copper, leading to accumulation of toxic level of copper in many tissues and
organs like liver, brain, eyes, kidneys, etc.
Copper builds up in these organs , over time can cause life-threatening
organ damage.
Discovered by “Samuel alexander kinnier wilson”.
Most commonly present between 6 to 40 years age group.
 Genetics of the disease

Cause is “mutation in the ATP7B gene”, located on chromosome 13, that

encodes an ATPase metal ion transporter that localizes to the Golgi region of
the hepatocytes .
Incidence of the disease is approximately 1 per 30,000 population.
About 1 in 100 people are asymptomatic carrier.
 Pathology
Normally, after hepatocellular uptake, copper will bind to a globulin protein in liver called
apoceruloplasmin to form ceruloplasmin, which is later SECRETED into plasma, where
it accounts 90-95% of plasma copper (in bounded form) & also EXCRETE copper into
bile.
Without APT7B activity, copper can’t be passed on to apoceruloplasmin and therefore
can’t be excreted into bile which is the primary route for copper elimination from the
body. Thus copper accumulates progressively into the hepatocytes leading to free
radicals formation and hepatocytes injury.
Copper begins to escapes from overloaded and damaged hepatocytes into the
circulation(unbounded free copper)
Copper also deposited in many other tissues such as brain, cornea, kidneys, bones, joints
and parathyroid gland , red blood cells where it causes tissue damage through the same
mechanism that causes injury to hepatocytes.
 CLINICAL MENIFESTATION
(from asymptomatic carrier to sever organ damage).
o Hepatic:
Hepatomegaly or hepatosplenomegaly
Acute and chronic hepatitis
Acute liver failure
Compensated or decompensated
cirrhosis (Ascites, portal HTN, bleeding
varices)
o Neurologic;
 Deterioration in school performance (school age group)
 Dysarthria (difficulty speaking) (in school age)
 Dysgraphia (difficulty in writing) (in school age)
 Dystonia (abnormal posture of limbs)
 Dysphagia (difficulty in swallowing)
 Termers, seizure
 Excessive salivation
 Delirium, confusion, dementia
 Ataxia (Abnormal coordination movements)
 Parkinsonism (mask like face etc)
 MENIFESTATION
o Psychiatric; o Skeletal;
 Emotional/Behavioral changes  Premature osteoporosis
 Anxiety  Arthritis
 Depression
 Psychosis
o Gynecological;
o Ocular;  Irregular menses
 Infertility
 Keyser-Fleisher ring
 Sunflower cataract  Repeated miscarriage
 CLINICAL
o Blood o Others;
 Hemolytic anemia  Pancreatitis
 CLINICAL STAGES
Progress through 4 clinical stages.
1) Asymptomatic accumulation of copper in liver, begins when patient is
born.
2) Either Asymptomatic or present with Hemolytic anemia or Liver failure.
3) Copper accumulation in brain.
4) Progressive neurological disease.
 DIAGNOSIS
 CBC= hemolytic anemia (coombs negative)
 Slit-lamp examination =Keyser-Fleisher ring (copper deposition on Descemet membrane of
cornea) 50-60% of the pt
 serum ceruloplasmin = LOW(<20mg/dl)
 serum copper = mostly LOW (due to deposition) but can be Normal/High.
 24 hr urinary copper = INCREASED (>100mcg)
 Hepatic copper concentration = INCREASED (>250mcg/g dry weight)
 Genetic testing (standard of screening in family members)
 Liver biopsy =copper deposition, macro-necrosis & cirrhosis of hepatocytes
 MRI brain =atrophy or cavitation of basal ganglia, and involvement of putamen, thalami,
and brainstem.
 X-ray Bones & Joints= Osteopnia, Arthopathy ,Articular abnormality, Osteomalacia & Rickets
 Keyser-Fleisher ring
(copper deposition on Descemet membrane of cornea)
 MRI brain

• Hyperintensity in tegmentum of midbrain

except the “red nucleus” forming eyes.
• Preservation of hyperintensity in lateral
portion of par reticulata of substantia nigra
forming “ears”
 TREATMENT

• LOWER INTAKE OF COPPER-RICH FOOD

Liver
Shellfish
Mushroom
Chocolates
 TREATMENT
Pencillamin ;(chelator)
 promotes copper excretion in urine
 Treatment is lifelong
 Always given with pyridoxine(vit.B6) to minimize the side effects.
 Never give as initial therapy in those with neurological manifestation.
Trientine ;(chelator)
 promote urinary copper excretion
 Patient intolerant to Pencillamin
Oral Zinc Acetate;
 decrease copper absorption from gut and increase fecal excretion.
 make non- toxic copper complexes within hepatocytes
 used in pre-symptomatic maintenance phase
Ammonium tetra thiomolybdate;
Treatment of choice in those with neurological symptoms (with zinc salts)
 make complexes with dietary copper – reduce absorption
 make complexes with free plasma copper - excreted in bile
Liver Transplant:
 when acute liver failure or DCLD unresponsive to therapy (curative treatment)
THANK YOU