[Clinicopathological features of Wilson disease: report of 29 cases]

To summarize the clinicopathological manifestations of Wilson disease(WD) so as to improve its recognition.

A total of 29 WD cases were retrospectively analyzed, including clinical presentations, liver function test, serum ceruloplasmin, 24 hour urinary copper excretion, ATP7B gene analysis and liver histology. All cases were diagnosed from January 2007 to October 2012 at Third Hospital of Hebei Medical University and China-Japan Friendship Hospital.

There were 18 males and 11 females with an average age of 25.9 years. The major clinical symptoms included fatigue (n = 18, 62.1%), abdominal distension (n = 4,13.8%) and pruritus (n = 4, 13.8%). The common physical signs were hepatomegaly (n = 11, 37.9%), splenomegaly(n = 15, 51.7%) and ascites (n = 4, 13.8%). The laboratory examinations included abnormal liver function (n = 29, 100%), high level of 24-hour urinary copper excretion (n = 29, 100.0%), low serum ceruloplasmin (n = 24, 82.8%) and Kayser-Fleischer ring (n = 8, 27.6%). ATP7B gene mutations were at exons 5, 8, 11, 12, 16 and 18. The earliest histologic abnormalities of liver included steatosis (both microvesicular and macrovesicular). Timm's stain showed positive or negative staining. There was no or focal hepatocellular necrosis in liver. During chronic hepatitis phase, the major changes included inflammatory cells infiltration in portal area with biliary epithelium degeneration. The periportal area hepatic cells were swollen, cytoplasm slightly stained and accompanied with some copper particles deposition and cholestic changes. There were many spotty or focal lesion of necrosis in liver. During cirrhotic phase, portal area became enlarged by fibrotic tissue, numerous copper particles deposited in wide fibrous septa and small bile ducts were damaged and became proliferative. Hepatocytes around fibrous interval showed cholestatic changes and contained many copper particles. They diagnosed on the basis of clinical presentation(n = 6), clinical presentation and liver histology (n = 4) and clinical presentation, liver histology and gene analysis (n = 19).

There is a high misdiagnosis rate of WD based solely on clinical presentation. Cholestic changes around fibrous interval are common histologic features. The most common ATP7B gene mutations are compound heterozygotes in exons 16. Comprehensive evaluations of clinical presentation, liver histology and gene analysis are helpful for early diagnosis and timely treatment so that it helps to reduce the misdiagnosis and missed diagnosis rate of WD.