WILSON DISEASE

PRESENTED BY SALQA UROOJ

SUBMITTED TO DR SHAKIR 9(PT)
INTRODUCTION

 Wilson disease is an autosomal recessive disorder which result in

excessive copper accumulation in body
 Also called hepatolenticular degeneration
 It primarily affect three organs but affect other organs as well
 .mainly affected three organs are

LIVER BRAIN EYE

ETIOLOGY

 Wilson disease is caused by one of several mutation in ATP7B gene present on

chromosome 13
 This gene controls the protein transporter responsible for excreting excess copper into bile
and out of body
 These protein transporters are located in trans golgi network of liver and brain
 The major route for copper excretion is liver
 When mutation occurs in this gene transport of copper affected and it gets accumulated
mainly in liver and then spills into blood and to other organs sysrem
PATHOPHYSIOLOGY

 As in Wilson disease excess copper accumulate in body

 . Cu is the transition metal , excess of Cu lead to formation of toxic hydroxyl group and
increase oxidative stress in cell. This increase oxidative stress damage the cell and lead to
clinical manifestation of Wilson disease
 Cu is needed by body as a cofactor for some enzymes
 Cu enters the body through the digestive tract with the help of transporter protein in the
cell of small bowel (copper membrane transporter 1)
 This transporter help Cu move inside the cell where part of Cu is bound to metallothionein
and part is carried by ATOX1 to an organelle known as trans golgi network
 In response to rising cu level, an enzyme called ATP7A release Cu into the portal veins to
the liver
 Liver cells carry CMT1 protein and metallothionein , and then ATOX1 binds it inside the
cell
 Once here ATP7B links the Cu to ceruloplasmin and release it into bloodstream , removing
excess Cu by secreting it into bile
 Both the functions of ATP7B are dysfunctional in wilsin disease
1. Cu accumulate in the liver
2. Ceruloplasmin is secreted in form that lacks Cu and it rapidly degraded in bloodstream
 When Cu level overwhelm the proteins that normally bind it , it result in oxidative changes
through a process known as Fenton chemistry
 This damage result in chronic active hepatitis , fibrosis and cirrhosis
 The liver releases Cu into bloodstream that is not bound to ceruloplasmin
 This free Cu precipitate throughout the body particularly in kidney , eyes and brain
affecting areas responsible for movement coordination and neurocognitive processes such
as stimulating mood regulation
 Damage to the areas produce neuropsychiatric symptoms
PATHOPHYSIOLOGY
SYMPTOMS
HISTORY AND PHYSICAL

1. A family history (heritable disorder)

2. abdominal pain
3. Jaundice(because of liver involvement)
4. Weakness
5. Personality changes
6. Depression
7. Migraine
8. Insomnia
9. Seizure
10. chorea
1. Hemiballismus in history
2. Neuropsycatric symptoms including asymmetrical symptoms
3. Drolling
4. Ataxia
5. Mask like faces
6. Clumpsiness
7. Difficulty speaking
8. Spasticity
9. Muscle rigidity
10. Premature osteoarthritis
11. Renal symptos similar to fanconi and urolithiasis
Physical examination

On physical examination a patient may have symptoms of spleenomagaly,isolated

spleenomagaly ,or if disease has progress to what cirrhosis than the stigmata of chronic liver
disease may also be prominent
An eye examination may reveal kayser flescher ring on cornea
Skin findings include ,lunulai ceruleae (bluish discolouration at the base finger nail)
Eye appearance
STAGING

STAGE 2
STAGE 1 ACUTE REDISTRIBUTION OF CU
INITIAL ACCUMULATION OF CU IN WITHIN LIVER FOLLOWED BY
LIVER RELEASE INTO SYSTEMATIC
CIRCULATION

WILSON DISEASE

STAGE 3 STAGE 4
CHRONIC ACCUMULATION OF CU USE OF THE CHELATION THERAPY TO
INTO EXTRA HEPATIC TISSUE RESTORE CU BALANCE
INCLUDNG BRAIN
EVALUATION

1. Ceruloplsmin level less than 20mg/dl(normal 20mg/dl to 40mg/dl)

2. Urinary cu level greater than 100 mcg/dl
3. Ceruloplasmin +urinary cu level +kayser Fleischer =diagnosed Wilson disease
4. Liver biopsy for liver cu level (most accurate)
5. Positive result is a cu level greater than 250mcg/gm of dry liver tissue
6. MRI for brain involvement (MRI may demonstrate the characteristics ;face of the giant
panda pattern)
7. Liver function test are deranged with elevated AST and ALT levels
MRI IMGING
TREATMENT

 Mainstay therapy for Wilson disease is cu chelation therapy with penicillamine and
trientine
 Trientine is preffered because of fewer side effects
 Oral zinc (compete for obsorption with copper)
 If liver cirrhosis than trans jungular intra hepatic porto systemic shunt or liver transplant
 Diet low in copper
 For muscle rigidity ,spasticity ; baclofene ,anti cholinergic ,GABA antagonists and
levodopa
 Physiotherapy and occupational therapy for neurological form of disease
TREATMENT FOR NEUROLOGICAL
SYMPTOMS OF WILSON DISEASE
PHYSIOTHERAPY ASSESSMENT
PHYSIOTHERPY EXERCISES