4. What Causes Wilson Disease?
Wilson disease is caused by mutations in the ATP7B gene.
This gene makes an enzyme that is involved in copper transport.
When the enzyme is mutated (not working properly) copper accumulates in the liver and brain and becomes toxic .
MUTATIONS ON Chromosome 13

5. Wilson Disease Pathogenesis

6. How Does it Run in Families?
Wilson disease is inherited in an autosomal recessive pattern.
Affected individuals have mutations in both copies of ATP7B
Carriers (mutation in only one copy) do not have symptoms

8. Wilson Disease Clinical spectrum Diagnostic tests Treatment options
Hepatic
Neuropsychiatric
Other
Diagnostic tests
Blood tests
Urine tests
Liver biopsy
Genetic testing
Treatment options
General chelators
Metallothionein inducers
Liver Transplantation
Follow-up
Blood tests
Urine tests

9. Wilson Disease Hepatic Manifestations
Asymptomatic hepatomegaly
Persistently abnormal AST and ALT
Fatty liver
Cirrhosis
Acute hepatitis
Similar to viral or autoimmune etiologies
Acute liver failure
Coomb’s negative hemolytic anemia
Acute renal failure
Aminotransferases abnormal in most patients with Wilson disease except at early age. Elevation is usually mild and does not correlate with severity of liver disease.

11. Kayser-Fleischer Rings
Copper deposited in Decemet’s membrane. Slit lamp required in most patients with suspected Wilson Disease % of patients with liver disease. 95% of patients with neurologic disease. Chronic cholestatic diseases associated with K-F rings. WD= K-F rings + low ceruloplasmin

12. Wilson Disease Coombs-negative hemolytic anemia
Rapid progression to renal failure
Modest rise in AST/ALT (< 2000 IU/L)
Normal or markedly subnormal alkaline phosphatase (< 40 IU/L)
Serum ceruloplasmin usually decreased
Serum and urine copper increased

14. Wilson Disease Histopathology
Chronic hepatitis
Fatty infiltration
Cirrhosis
Variety of findings: lymphocytic infiltration, fatty infiltration, ballooning with apoptosis, fibrous septae/cirrhosis.
Apoptosis

18. Case presentation
An eight-year-old African boy, previously well, was referred to our unit on account of nephrotic syndrome. He had presented to our emergency department a day before with as cites, facial swelling and reduced urinary output in the preceding two weeks. After two days of hospitalization, he became deeply jaundiced with worsening of the generalized edema.

19. In the second week of hospitalization, our patient developed tremors of his hands while at rest and when reaching for objects. He became clumsy when performing chores involving the use of his hands. His gait was noticed to be shuffling with a tendency to fall forward when trying to walk. At the same time, his face retained a wry smile and his speech became slurred and dysarthric.

20. He was also noticed to be emotionally labile; he cried inconsolably when asking for food. He was reviewed by a pediatric neurologist who pointed out the possible presence of Kayser-Fleischer (KF) rings on both eyes. A slit-lamp examination by an ophthalmologist promptly revealed the presence of both KF rings and sunflower cataracts.

22. Initial investigations showed proteinuria of grade 1+ Table 1 shows the results for his liver function test during hospitalization. His serum electrolytes, urea and creatinine were within the normal reference
Serology for human immunodeficiency virus, hepatitis B and hepatitis C viruses were negative. A serum sample for caeruloplasmin level was returned as having 5mg/dL of caeruloplasmin, using an immunoturbidimetric method (reference range: 25 to 45mg/dL). range.

23. 64-83 g/l 35-52 g/l 13-40 U/L 10-59U/L 53-128U/L 1-30U/L
,<0.3mg/dl
64-83 g/l
35-52 g/l
13-40 U/L
10-59U/L
53-128U/L
1-30U/L

24. Using the scoring system proposed by the 8th International Meeting of Wilson Disease and Menkes Disease, our patient achieved a score of 6 (compatible neuropsychiatric features = 2; K-F rings = 2 and caeruloplasmin level of 5mg/dL =2) and a diagnosis of WD was made.

25. Thank you
إعداد :
أحمد رفيق الدلو
حسين محمد دكة