Definition of Wilson disease ,presentation ,diagnosis ,treatment ,prognosis

1. Children with difficulty in
speech and writing associated
with pallor and abnormal liver
function tests and seizures

2. 13yr old boy
history
• Difficulty in speech and writing for 4
years and also on walking for 1 year.
• Difficulty to perform any work by
hands for 6 months
• His speech was low volume slurred
and monotonous
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3. Examination
• Splenomegaly and bilateral gynaecomastia.
• Muscle tone was mildly increased, and gait
was limping.
• Slit lamp examination of eye revealed
bilateral Kayser-Fleischer ring with normal
visual acuity.
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4. MRI T2 & T1-Weighted Image
Hyperintensity & Hypointensity in Bilateral
Basal Ganglia & Putamen Region
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5. Normal MRI of the brain
Axial MRI image through the basal ganglia. Included in the
basal ganglia are the caudate and putamen, globus pallidus
externus (GPe), and globus pallidus internus (GPi).
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6. 11yr old boy
history
• Progress pallor , lassitude ,mildly
jaundice for the last 2 months
• Dysarthria
• Salivation
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7. Examination
• Pallor , Jaundiced ,palmer erythema
• Hepatomegaly
• Postural tremor, dysdiadochokinesia
• Dysarthria, Gait disturbances
• The Kayser-Fleischer ring is found on
slit lamp examination of the eye
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8. Kayser-Fleischer ring
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9. Laboratory investigations
• Low serum albumin(26 gram/L)
• Increased alanine transaminase
( A.L.T=57 U/L)
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10. Ultrasonogram
Hepatobiliary system revealed coarse hepatic
tissue echotexture with splenomegaly.
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11. Liver scan
Slightly :
• Nonuniform radiotracer distribution in
the liver
• Increased bony uptake.
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12. Additional laboratory investigations
• Serum caeruloplasmin level was 11.51
mg/dl.
• 24 hours urinary copper excretion was
150 microgram per day
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13. 17 years old boy
history
• History of seizures for last 7 days
• Generalized tonic clonic in nature.
• For last 2 days he was having multiple
seizure episodes without regaining of
consciousness in between.
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14. Prior history
• Behavioral disturbances in the form of :
- Disinterest in the surroundings
- Decreased interaction with friends
and relatives
- Occasional outburst of temper for last
4 months was present
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15. Cont.
• Speech and gait difficulties for last 2
months.
• There was no history of
headache, vomiting, visual disturbances
or focal deficits.
• None of his siblings had similar illness.
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16. General examination
• Vitals were stable
• No jaundice or flaps
• Abdominal examination did not reveal
organomegaly or free fluid.
• On general examination Kayser-Fleischer
rings were present in cornea
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17. Neurological examination
• Mute, having mask like faces, drooling
of saliva and dystonic tongue
• Generalized cogwheel rigidity in all 4
limbs including axial musculature
• Postural tremors of both upper limbs
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18. Cont.
• Hyperreflexia, extensor planters and
normal muscle strength.
• Sensory and cerebellar system
examination was unremarkable
• Ophthalmological exam showed Kayser-
Fleischer ring on slit lamp
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19. Diagnosis?
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20. Wilson disease
(Hepatolenticular Degeneration)
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan hospital
Sharjah ,UAE
saadsalani@yahoo.com

21. Wilson disease
(Hepatolenticular degeneration)
Is an autosomal recessive disorder
characterized by:
1.Degenerative changes in the brain
2. Liver disease
3.Kayser-Fleischer rings in the cornea
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22. Autosomal recessive inborn error of copper
transport
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23. The incidence
1/50,000-100,000 births
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24. Introduction
• The abnormal gene for Wilson disease is
on chromosome 13; linkage studies have
assigned the Wilson disease locus to
chromosome 13 at q14-q21.
• The gene encodes amino acid structural
motifs consistent with a role in copper-
binding, cation-transporting P-type
ATPase .
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25. Basic mechanism
• Relates to decreased excretion of biliary
copper, owing partly to a lysosomal
defect of the liver cells
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26. Healthy subjects: intake and excretion
is well balanced
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27. Normal absorption and distribution of
copper
Cu = copper, CP = ceruloplasmin, green = ATP7B carrying
copper.
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28. Pathogenesis
Defective mobilization of copper
from lysosomes in liver cells
↓ Oxidant injury to
Relentless accumulation hepatocyte
of copper in the liver → mitochondria
↓ ↓
Copper then escapes the liver Lipid peroxidation of
the mitochondria
to damage other organs
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29. Clinical Manifestations
Forms of hepatic disease:
• Include :
1.Asymptomatic hepatomegaly
(with or without splenomegaly)
2.Subacute or chronic hepatitis
3.Fulminant hepatic failure.
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30. Cont.
Other manifestations of Wilson disease
include:
* Cryptogenic cirrhosis
* Portal hypertension,
* Ascites
* Edema,
* Variceal bleeding
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31. Cont.
*Other effects of hepatic dysfunction :
- Delayed puberty
- Amenorrhea,
- Coagulation defect
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32. Clinical Manifestations
Neurologic and psychiatric disorders
• Intention tremor
• Dysarthria
• Dystonia
• Deterioration in school performance, or
behavioral changes.
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33. Clinical Manifestations
other features
• Hemolysis may be an initial manifestation
• Manifestations of Fanconi syndrome and
progressive renal failure
• Unusual manifestations include:
- Arthritis
- Endocrinopathies, such as
hypoparathyroidism
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34. Diagnosis
Wilson disease should be considered in children and
teenagers with :
1.Unexplained acute or chronic liver disease,
2. Neurologic symptoms of unknown cause,
3. Acute hemolysis
4.Psychiatric illnesses,
5. Behavioral changes,
6.Fanconi syndrome
7.Unexplained bone disease.
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35. Tests performed for the diagnosis of
Wilson disease
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36. Cont.
• The best screening test is to measure
the serum ceruloplasmin level.
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37. Cont.
• Serum copper level :
>100 μg /day and often up to 1,000 μg or
more per day.
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38. Liver biopsy
• Is of value for :
1.Examination of the histology
2.Measurement of the hepatic copper
content (normally <10 μg/g dry weight).
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39. Screening family members of patients
Should include determination of :
1.Serum ceruloplasmin level
2. Urinary copper excretion.
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40. The first signs due to :
• Hepatic : (40% )
• Neurological : (35% )
• Psychiatric , Renal, Hematological ,
Endocrine ( In the remainder)
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41. Wilson's disease patients before treatment:
reduced excretion and retention
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42. Treatment
Copper-chelating agents:
• Oral administration of penicillamine (β, β-
dimethylcysteine) in a dose of :
* 0.5-0.75 g/day for patients younger than
10 yr.
*1 g/day in two doses before meals for
adults
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43. Wilson's disease patients on chelator therapy:
enhanced urinary excretion of copper
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44. Toxic effects of penicillamine
• Uncommon and consist of
1.Hypersensitivity reactions (Goodpasture
syndrome, systemic lupus
erythematosus, polymyositis),
2. Interaction with collagen and elastin
3.Deficiency of other elements such as zinc
4.Aplastic anemia
5. Nephrosis
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45. Treatment (cont.)
• For those patients who are unable to
tolerate penicillamine, triethylene
tetramine dihydrochloride
(Trien, TETA, trientine) at a dose of 0.5-2
g/24 hr is an acceptable alternative.
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46. Treatment (cont.)
• Zinc has also been used as adjuvant
therapy or as maintenance therapy owing
to its unique ability to impair the
gastrointestinal absorption of copper.
• Zinc acetate is given in adults at a dose
of 25 to 50 mg three times a day .
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47. Wilson's disease patients on zinc therapy:
enhanced fecal excretion of copper
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48. Remember
• Foods such as:
liver, shellfish, nuts, and chocolate
should be avoided
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49. Prognosis
• Untreated patients with Wilson disease die
of the hepatic, neurologic, renal, or
hematologic complications.
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50. Cont.
• The prognosis for patients receiving
prompt and continuous d- penicillamine is
variable and depends on :
* Time of initiation
* Individual responsiveness .
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51. Liver transplantation
• Should be considered for patients with:
1. fulminant liver disease
2. decompensated cirrhosis
3. progressive neurologic disease
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52. In asymptomatic siblings of affected
patients
Early institution of chelation therapy can
prevent expression of the disease.
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53. Remember Wilson disease
1.If "routine liver function tests" are
inexplicably abnormal in a child
2.In a child with haemolysis and negative
Coombs test
3. Changes in mood or school performance
in a teenager, especially with speech
slurring
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54. .
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55. References
• http://www.eurowilson.com/en/living/guide/pathw
ay/index.phtml
• http://www.wilsonsdisease.org/
• http://www.ars.usda.gov/Services/docs.htm?docid
=17477
• http://emedicine.medscape.com/article/183456-
clinical
• http://www.eurowilson.org/data/pdf/For-
medical-professionals.pdf
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