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

Wilson Disease Pathogenesis

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

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

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.

Kayser-Fleischer Rings Copper deposited in Decemet’s membrane. Slit lamp required in most patients with suspected Wilson Disease. 50-62% 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

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

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

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.

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.

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.

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.

64-83 g/l 35-52 g/l 13-40 U/L 10-59U/L 53-128U/L 1-30U/L 0.1-1.2,<0.3mg/dl 64-83 g/l 35-52 g/l 13-40 U/L 10-59U/L 53-128U/L 1-30U/L

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.

Thank you إعداد : أحمد رفيق الدلو حسين محمد دكة