Background & Aims: Cholestatic liver disease is a leading referral to pediatric liver transplant centers. Inherited disorders are the second most frequent cause of cholestasis in the first months of life. Methods: We retrospectively characterized the genotype and phenotype of 166 participants with intrahepatic cholestasis,and re-analyzed phenotype and WES data from patients with previously undetermined genetic etiology for newly published genes and novel candidates. Functional validations of selected variants were conducted in cultured cells. Results: Overall, we identified disease causing variants in 31% (52/166) of our study participants. Of the 52 individuals, 18 (35%) were metabolic liver diseases, 9 (17%) were syndromic cholestasis, 9 (17%) were progressive familial intrahepatic cholestasis, 3 (6%) were bile acid synthesis defects, 3(6%) were infantile liver failure and 10 (19%) were phenocopy of intrahepatic cholestasis. By reverse phenotyping, we identified a de novo variant c.1883G>A in FAM111B of a case with high glutamyl transpeptidase (GGT) cholestasis. By reanalyzing WES data, two patients were newly solved, which had compound heterozygous variants in recently published genes KIF12 and USP53, respectively. Our additional search for novel candidates in unsolved trio families revealed four potential novel candidate genes (NCOA6, CCDC88B, USP24 and ATP11C), among which the patients with variants in NCOA6 and ATP11C recapitulate the cholestasis phenotype in mice model. Conclusions: In a single center pediatric cohort, we identified monogenic variants in 22 known human intrahepatic cholestasis or phenocopy genes, explaining up to 31% of the intrahepatic cholestasis patients. Rigorous analysis of WES data of well-phenotyped patients with intrahepatic cholestasis leads to a broader understanding of gene-specific phenotypic spectra as well as monogenic candidate gene identification.
Background The aim of this study was to characterize patients with multiple rare-earth magnet ingestion in a single-pediatric medical center, reveal the harm of rare-earth magnets foreign bodies in digestive tract, and develop a clinical management algorithm. Methods This was a retrospective review of patients with rare-earth magnets foreign bodies in digestive tract admitted to a university-affiliated pediatric medical center in China, between January 2016 to December 2019, with a subset of medical data including clinical symptoms, signs, treatments and outcomes. Results A total of 51 cases were included in this study, including 36(70.6%) males and 15(29.4%) females. The magnets were passed naturally in 24(47.1%) patients and removed by intervention in 27(52.9%) patients, including five(9.8%) cases by endoscopy and 22(43.1%) cases by surgery. 22(43.1%) cases had gastrointestinal obstruction, perforation, and fistula. Compared with the non-surgical group, the proportion of males in the surgical group was higher (21/23 vs 15/28, p=0.004), and the visiting time to hospital was longer (80(72) vs 26(5), hours, p=0.008). Conclusions The rate of surgical intervention is high in multiple rare-earth digestion cases and the consequences are serious, and a more efficient management algorithm for these cases should be needed. A policy for strictly restricted or prohibited the sale of the toys with multiple rare-earth magnets needed to put into the agenda. Trial registration The study will be retrospectively registered.
Background The aim of this study was to characterize patients who ingested multiple rare-earth magnets, reveal the harm of rare-earth magnet foreign bodies in the digestive tract, and develop a clinical management algorithm. Methods This was a retrospective review of patients with rare-earth magnet foreign bodies in the digestive tract admitted to a university-affiliated pediatric medical center in China, between January 2016 and December 2019; the subset of medical data evaluated included clinical symptoms, signs, treatments and outcomes. Results A total of 51 cases were included in this study, including 36(70.6%) males and 15(29.4%) females. The magnets were passed naturally in 24(47.1%) patients and removed by intervention in 27(52.9%) patients, including 5(9.8%) cases by endoscopy and 22(43.1%) cases by surgery. Twenty-two(43.1%)cases had gastrointestinal obstruction, perforation, and fistula. Compared with the non-surgical group, the time of the surgical group from ingestion to arriving at the hospital was longer([80(5-336) vs 26(2-216)]hours, p<0.001)while there was no significant difference in the mean age or the number of magnets swallowed. Conclusions Magnets are attractive to children, but lead to catastrophic consequences including gastrointestinal obstruction, perforation, and surgical interventions when ingested multiple magnets. Endoscopic resection should be urgently performed in the presence of multiple magnets as early as possible within 24 hours, even in asymptomatic patients.
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