Wilson disease

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

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  • Most patients with Wilson disease have decreased ceruloplasmin levels
  • (usually <40 μg/ day)
  • In Wilson disease, hepatic copper content exceeds 250 μg/g dry weight. In healthy heterozygotes, levels may be intermediate.
  • In response to d-penicillamine, urinary copper excretion markedly increases and there may be slow clinical improvement.
  • Wilson disease

    1. 1. Children with difficulty inspeech and writing associatedwith pallor and abnormal liver function tests and seizures
    2. 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 monotonous10/30/2012 Prof. Dr. Saad S Al Ani 2
    3. 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. 10/30/2012 Prof. Dr. Saad S Al Ani 3
    4. 4. MRI T2 & T1-Weighted ImageHyperintensity & Hypointensity in Bilateral Basal Ganglia & Putamen Region10/30/2012 Prof. Dr. Saad S Al Ani 4
    5. 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).10/30/2012 Prof. Dr. Saad S Al Ani 5
    6. 6. 11yr old boyhistory• Progress pallor , lassitude ,mildly jaundice for the last 2 months• Dysarthria• Salivation10/30/2012 Prof. Dr. Saad S Al Ani 6
    7. 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 eye10/30/2012 Prof. Dr. Saad S Al Ani 7
    8. 8. Kayser-Fleischer ring10/30/2012 Prof. Dr. Saad S Al Ani 8
    9. 9. Laboratory investigations • Low serum albumin(26 gram/L) • Increased alanine transaminase ( A.L.T=57 U/L)10/30/2012 Prof. Dr. Saad S Al Ani 9
    10. 10. UltrasonogramHepatobiliary system revealed coarse hepatic tissue echotexture with splenomegaly.10/30/2012 Prof. Dr. Saad S Al Ani 10
    11. 11. Liver scanSlightly :• Nonuniform radiotracer distribution in the liver• Increased bony uptake.10/30/2012 Prof. Dr. Saad S Al Ani 11
    12. 12. Additional laboratory investigations• Serum caeruloplasmin level was 11.51 mg/dl.• 24 hours urinary copper excretion was 150 microgram per day10/30/2012 Prof. Dr. Saad S Al Ani 12
    13. 13. 17 years old boyhistory• 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.10/30/2012 Prof. Dr. Saad S Al Ani 13
    14. 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 present10/30/2012 Prof. Dr. Saad S Al Ani 14
    15. 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.10/30/2012 Prof. Dr. Saad S Al Ani 15
    16. 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 cornea10/30/2012 Prof. Dr. Saad S Al Ani 16
    17. 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 limbs10/30/2012 Prof. Dr. Saad S Al Ani 17
    18. 18. Cont.• Hyperreflexia, extensor planters and normal muscle strength.• Sensory and cerebellar system examination was unremarkable• Ophthalmological exam showed Kayser- Fleischer ring on slit lamp10/30/2012 Prof. Dr. Saad S Al Ani 18
    19. 19. Diagnosis?10/30/2012 Prof. Dr. Saad S Al Ani 19
    20. 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. 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 cornea10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 21
    22. 22. Autosomal recessive inborn error of copper transport10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 22
    23. 23. The incidence 1/50,000-100,000 births10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 23
    24. 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 .10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 24
    25. 25. Basic mechanism • Relates to decreased excretion of biliary copper, owing partly to a lysosomal defect of the liver cells10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 25
    26. 26. Healthy subjects: intake and excretionis well balanced10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 26
    27. 27. Normal absorption and distribution of copper Cu = copper, CP = ceruloplasmin, green = ATP7B carrying copper.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 27
    28. 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 organs10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 28
    29. 29. Clinical ManifestationsForms of hepatic disease: • Include : 1.Asymptomatic hepatomegaly (with or without splenomegaly) 2.Subacute or chronic hepatitis 3.Fulminant hepatic failure.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 29
    30. 30. Cont. Other manifestations of Wilson disease include: * Cryptogenic cirrhosis * Portal hypertension, * Ascites * Edema, * Variceal bleeding10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 30
    31. 31. Cont. *Other effects of hepatic dysfunction : - Delayed puberty - Amenorrhea, - Coagulation defect10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 31
    32. 32. Clinical ManifestationsNeurologic and psychiatric disorders• Intention tremor• Dysarthria• Dystonia• Deterioration in school performance, or behavioral changes.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 32
    33. 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 hypoparathyroidism10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 33
    34. 34. DiagnosisWilson 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.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 34
    35. 35. Tests performed for the diagnosis of Wilson disease10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 35
    36. 36. Cont. • The best screening test is to measure the serum ceruloplasmin level.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 36
    37. 37. Cont.• Serum copper level : >100 μg /day and often up to 1,000 μg or more per day.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 37
    38. 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). 10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 38
    39. 39. Screening family members of patients Should include determination of : 1.Serum ceruloplasmin level 2. Urinary copper excretion.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 39
    40. 40. The first signs due to : • Hepatic : (40% ) • Neurological : (35% ) • Psychiatric , Renal, Hematological , Endocrine ( In the remainder)10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 40
    41. 41. Wilsons disease patients before treatment: reduced excretion and retention10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 41
    42. 42. TreatmentCopper-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 adults10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 42
    43. 43. Wilsons disease patients on chelator therapy:enhanced urinary excretion of copper10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 43
    44. 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. Nephrosis10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 44
    45. 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.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 45
    46. 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 .10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 46
    47. 47. Wilsons disease patients on zinc therapy:enhanced fecal excretion of copper10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 47
    48. 48. Remember• Foods such as: liver, shellfish, nuts, and chocolate should be avoided10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 48
    49. 49. Prognosis• Untreated patients with Wilson disease die of the hepatic, neurologic, renal, or hematologic complications.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 49
    50. 50. Cont.• The prognosis for patients receiving prompt and continuous d- penicillamine is variable and depends on : * Time of initiation * Individual responsiveness .10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 50
    51. 51. Liver transplantation • Should be considered for patients with: 1. fulminant liver disease 2. decompensated cirrhosis 3. progressive neurologic disease10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 51
    52. 52. In asymptomatic siblings of affectedpatients Early institution of chelation therapy can prevent expression of the disease.10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 52
    53. 53. Remember Wilson disease1.If "routine liver function tests" are inexplicably abnormal in a child2.In a child with haemolysis and negative Coombs test3. Changes in mood or school performance in a teenager, especially with speech slurring10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 53
    54. 54. .10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 54
    55. 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.pdf10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 55
    56. 56. 10/30/2012 Wilson Disease Prof. Dr. Saad S Al Ani 56

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