Potential of the international scoring system for the diagnosis of Wilson disease to differentiate Japanese patients who need anti-copper treatment.

AIM: Patients with Wilson disease show complex clinical features. Accurate diagnosis at the initial clinical manifestation is important for patients to receive effective treatment with anti-copper agents. In this study, we assessed whether the international scoring system for the diagnosis of Wilson disease is a reliable tool for screening Japanese patients with primary copper toxicosis requiring anti-copper treatment. METHODS: Twenty-three Japanese patients suspected of Wilson disease were enrolled in this study. We performed long-range polymerase chain reaction to detect ATP7B mutations in this series. Finally, we retrospectively assessed the reliability of using a diagnostic score of 4 or more points as the cut-off for this scoring system. RESULTS: Ten patients were homozygous or compound heterozygous for ATP7B mutations including a novel mutation of 3837 bp deletion including 3 exons. The mutation would have been missed by the traditional analysis. Six patients were heterozygous for ATP7B mutations. Three of these six patients had additional diagnostic points. The other three patients were diagnosed as carriers of a mutant gene based on their low scores. One of the seven patients free from ATP7B mutation was affected by copper toxicosis. Though the score was 3 points based on increased urinary copper and copper-positive cirrhosis, anti-copper treatment promptly improved liver failure, which was likely due to idiopathic copper toxicosis. CONCLUSION: The international scoring system for diagnosis of Wilson disease is a fairly reliable tool for screening Japanese patients who need anti-copper treatment. Caution is needed for patients with possible idiopathic copper toxicosis because the maximal score is 4 points.

Current state of Wilson disease patients in central Japan.

OBJECTIVE: This study evaluated the current state of patients with Wilson disease in central Japan. PATIENTS AND METHODS: Between 1999 and 2007, 30 patients were diagnosed as having Wilson disease with an International Diagnostic Score of 4 or more. The phenotypes, genotypes and post-diagnostic courses of these patients were analyzed. RESULTS: Twenty-six patients had ATP7B mutations responsible for Wilson disease. Four patients had a single mutant chromosome. There were 2 major mutations of 2333 G>T and 2871 delC (40%), and 6 novel mutations (13%) in our patients. The first clinical manifestation was the hepatic form in 22, neurological form in 5, and hemolysis in 3 patients. The hepatic form was diagnosed around the age of 13 years, followed by neurological complication with a time lag of 9 years. Thus, some patients, especially patients with the neurological form, did not undergo early diagnostic tests including ATP7B analysis. During the post-diagnosis period, 3 patients were hospitalized for recurrent liver disease, and 2 patients committed suicide. One female patient died from acute hepatic failure associated with encephalopathy after fertilization therapy, while 2 male patients recovered from encephalopathy-free, prolonged hepatic failure after noncompliance with drug therapy. The King's Scores for liver transplantation were below the cut-off in both cases. CONCLUSION: To minimize delayed diagnosis, ceruloplasmin determination and ATP7B analysis may be recommended to patients showing hepatic damage of unknown etiology. At gene diagnosis, appropriate management of patients including compliance education and emotional care to prevent suicide might be important.

[Meckel's diverticulum and duplication of the alimentary tract].

Meckel's diverticulum and duplication of the alimentary tract are very important as the congenital anomalies of ileum. As these two diseases have the common clinical characteristics such as sex, age, symptoms and complications, it is often difficult to diagnose before surgery. This report describes and compared the clinical aspects of Meckel's diverticulum and duplication of the alimentary tract, which were experienced at Nagoya University Hospital and Kariya Toyota General Hospital.

Large duodenal somatostatinoma in the third portion associated with severe glucose intolerance.

A 51-year-old man was admitted with hyperglycemia and a duodenal tumor. Although his glycemic control was poor, basal C-peptide levels were not suppressed. Further examination revealed a mass measuring 7.8 cm in diameter in the third portion of the duodenum. Duodenectomy revealed a slow-growing sessile tumor located near Treitz's ligament. The immunohistochemical profile of sections of the specimen revealed the presence of somatostatin. The patient's serum somatostatin was elevated to 300 pg/ml preoperatively, but was reduced to 10 pg/ml postoperatively. Glycemic control also normalized after the operation.

Characteristics and prognosis of hepatocellular carcinoma detected in sustained responders to interferon therapy for chronic hepatitis C.

Interferon (IFN) therapy allows the eradication of hepatitis C virus (HCV) in some part of patients with chronic hepatitis C which is major cause of hepatocellular carcinoma (HCC). To clarify characteristics and prognoses of HCC detected in these patients (sustained responders to IFN), we compared HCC in sustained responders with HCC detected in patients without a sustained response (non-sustained responders). Characteristics and prognoses were compared in nine cases of HCC detected in sustained responders after IFN therapy and 61 cases of HCC detected in non-sustained responders at one of five our institutions. HCC in sustained responders often were larger (P=0.0051), less differentiated tumor (P=0.0084) than HCC in non-sustained responders when it was detected. No differences were observed in overall survival rate between sustained responders and non-sustained responders, but disease-free survival was higher in cases of HCC in sustained responders (P=0.0494). HCC detected in sustained responders often appear more advanced when detected than HCC in non-sustained responders, but recurrence seems to be less frequent when the initial HCC is treated sufficiently.