Severe early-onset Wilson disease caused by a common pathogenic variant in the Bukharan Jewish population in Israel.

BACKGROUND: Wilson disease is caused by pathogenic variants in the ATP7B gene which encodes a copper-transporting ATPase. AIMS: Describe a common founder pathogenic variant among Bukharan Jews and to assess its prevalence, clinical features, and outcome. METHODS: The cohort consisted of patients of Bukharan Jewish descent diagnosed with Wilson disease at a tertiary pediatric medical center in 2013-2018. Clinical and genetic data were collected and analyzed. RESULTS: Six patients from 4 unrelated families who were homozygous for the c.3784G > T p.(Val1262Phe) pathogenic variant in ATP7B were identified. Five presented with elevated aminotransferase levels, and one, with acute liver failure. Mean age at diagnosis was 8.7 years (5-12.5). Serum ceruloplasmin level was extremely low in all patients (1.9-7 mg/dL; mean 3.2(. The variant was identified in a heterozygous state in 5/153 Bukharan Jews; 2/33 from our local exome database and 3/120 healthy unrelated Bukharan Jews in another cohort, for an estimated carrier frequency of ∼1:30. CONCLUSIONS: We report a common founder pathogenic variant in the ATP7B gene among Bukharan Jews associated with severe early-onset Wilson disease. Given the clinical severity, high frequency of the variant, and being a treatable disease, its inclusion in pre-symptomatic screening in the Bukharan Jewish community should be considered. Furthermore, WD should be part of future genetic newborn screening programs in Israel and worldwide, to enable early treatment and prevention of future life-threatening complications.

Endoscopic Findings in Children with Isolated Lower Gastrointestinal Bleeding.

BACKGROUND/AIMS: Colorectal polyps are a common cause of lower gastrointestinal bleeding in children. Our aim was to study the causes of isolated lower gastrointestinal bleeding and to analyze the characteristics of the colorectal polyps found in our cohort. METHODS: We retrospectively reviewed colonoscopic procedures performed between 2007 and 2015. Children with isolated lower gastrointestinal bleeding were included in the study. RESULTS: A total of 185 colonoscopies were performed for isolated lower gastrointestinal bleeding. The median patient age was 8 years, and 77 patients (41.6%) were found to have colonic polyps. Normal colonoscopy findings were observed and acute colitis was detected in 77 (41.6%) and 14 (7.4%) patients, respectively. Single colonic polyps and 2-3 polyps were detected in 73 (94.8%) and 4 (5.2%) patients with polyps, respectively. Of the single polyps, 69 (94.5%) were juvenile polyps, among which 65 (94.2%) were located in the left colon. CONCLUSION: Single left-sided juvenile polyps were the most common cause of isolated lower gastrointestinal bleeding in our study. It was rare to find multiple polyps and polyps proximal to the splenic flexure in our cohort. A full colonoscopy is still recommended in all patients in order to properly diagnose the small but significant group of patients with pathologies found proximal to the splenic flexure.