A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations.

Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

OBJECTIVE: Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. METHODS: The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. RESULTS: The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. CONCLUSION: Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

A novel deletion mutation within the carboxyl terminus of the copper-transporting ATPase gene causes Wilson disease.

In patients with Wilson disease (WD), an autosomal recessive disorder, toxic accumulation of copper results in fatal liver disease and irreversible neuronal degeneration. ATP7B, the gene mutated in WD, contains 21 exons and encodes a copper-transporting ATPase. In this study, all exons of the ATP7B gene of nine WD patients were screened for alterations by conventional mutation detection enhancement (MDE) heteroduplex analysis, followed by direct sequencing of the regions that showed heteroduplex formation. For the first time, a novel deletion mutation (4193delC) in exon 21, causing a frameshift leading to premature truncation of the protein was detected in four of nine patients. The 4193delC removes several signals within the carboxyl terminal domain that may disrupt trafficking of ATP7B protein through trans-Golgi network at the cellular level.

Randomized trial of ligation versus combined ligation and sclerotherapy for bleeding esophageal varices.

BACKGROUND: Endoscopic band ligation combined with sclerotherapy has been postulated to be superior to ligation alone for the treatment of esophageal variceal bleeding. METHODS: A randomized trial of ligation versus combined ligation and sclerotherapy was designed to determine whether combined therapy results in faster eradication of varices compared to ligation alone. Sixty patients were randomized to undergo band ligation or ligation combined with injection of 1 to 2 mL of polidocanol (1%) into each variceal column immediately proximal to the previously placed bands. Therapy was repeated at 1- or 2-week intervals until variceal eradication was achieved. Follow-up endoscopy was performed at 3 months and then at 6-month intervals. RESULTS: The demographic and clinical characteristics of the 31 patients who underwent ligation were similar to those of the 29 who received combined treatment. Sixty percent of the patients had cirrhosis due to viral hepatitis. No significant differences were found between the combined and ligation alone groups in arresting active bleeding [9 of 9 (100%) vs. 6 of 7 (86%)], units of blood transfusion (3 +/- 0.8 vs. 2 +/- 0.6), number of sessions required to eradicate varices (3.8 +/- 0.5 vs. 3.6 +/- 0.4), treatment failure [2 (17%) vs. 4 (14%)], esophageal varix recurrence [6 (21.%) vs. 2 (6%)], gastric varices formation [4 (14%) vs. 1 (3%)], stricture [1 (3%) vs. 0 (0%)], recurrent bleeding [5 (17%) vs. 7 (23%)], other complications [10 (34%) vs. 9 (29%)], or death [3 (10%) vs. 7 (23%)] during a follow-up period of up to 36 months. CONCLUSIONS: Combined ligation and sclerotherapy does not reduce the number of endoscopic treatment sessions required for variceal eradication and offers no benefit over ligation alone. Because of the lack of benefit, the added procedure time, and the cost, we do not advocate combination therapy, and ligation alone remains the best endoscopic treatment.