Wilson's disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

AIM To determine the phenotypes and predominant diseasecausing mutations in Lebanese patients with Wilson's disease,as compared to regional non-European data.METHODS The clinical profile of 36 patients diagnosed in Lebanon was studied and their mutations were determined by molecular testing.All patients underwent full physical exam,including ophthalmologic slit-lamp examination ultrasound imaging of the liver,as well as measurement of serum ceruloplasmin and 24-h urinaryCu levels.In addition,genetic screening using PCR followed by sequencing to determine disease-causing mutations and polymorphisms in the ATP7B gene was carried on extracted DNA from patients and immediate family members.Our phenotypic-genotypic findings were then compared to reported mutations in Wilson's disease patients from regional Arab and non-European countries. RESULTS Patients belonged to extended consanguineous families.The majority were homozygous for the disease-causing mutation,with no predominant mutation identified. The most common mutation,detected in 4 out of 13families,involved the ATP hinge region and was present in patients from Lebanon,Egypt,Iran and Turkey.Otherwise,mutations in Lebanese patients and those of the region were scattered over 17 exons of ATP7B.While the homozygous exon 12 mutation Trp939Cys was only detected in patients from Lebanon but none from the regional countries,the worldwide common mutation H1069Q was not present in the Lebanese and was rare in the region.Pure hepatic phenotype was predominant in patients from both Lebanon and the region(25%-65%).Furthermore,the majority of patients,including those who were asymptomatic,had evidence of some hepatic dysfunction.Pure neurologic phenotype was rare. CONCLUSION Findings do not support presence of a founder effect.Clinical and genetic screening is recommended for family members with index patients and unexplained hepatic dysfunction.

Uric Acid;a Possible Mediator of the Adjuvant Effect of Alum in Mice Immunized with Ovalbumin

One proposed mechanism by which alum enhances an immune response is by its ability to induce an inflammatory response that results in the release of uric acid from necrotic cells. Uric acid is thought to be a mediator in enhancing the immune response. The aim of this study was to investigate the immunopotentiating effect of uric acid. Groups of BALB/c mice were injected intraperitoneally with ovalbumin, ovalbumin + alum, ovalbumin + uric acid, uric acid, alum, or allopurinol. Two other groups were pretreated with allopurinol and were given ovalbumin + alum, or ovalbumin + uric acid 24 hours later. An additional two groups served as controls. On days 4, 7 and 10 post-injection, the numbers of Interleukin 4(IL-4) and Interferon-γ (IFN-γ) secreting spleen cells were determined by the ELISPOT assay. Serum uric acid levels were determined using an autoanalyser and nitric oxide using the Greiss reagent. The groups that received alum + ovalbumin or uric acid + ovalbumin had the highest numbers of IL-4 and INF-γ secreting cells as compared to all the groups. Allopurinol administration one day prior to alum + ovalbumin or uric acid + ovalbumin resulted in a decrease in the number of IL-4 and INF-γ secreting cells when compared to alum+ ovalbumin or uric acid + ovalbumin allopurinol - untreated groups. Groups that received alum, alum + ovalbumin, uric acid, and uric acid + ovalbumin had high serum uric acid levels as compared to all the groups. All groups that received alum had the highest levels of nitric oxide when compared to the groups that were not given alum. In conclusion, it appears that uric acid might be a mediator in the adjuvant effect of alum.