ATP8B1, ABCB11, and ABCB4 Genes Defects: Novel Mutations Associated with Cholestasis with Different Phenotypes and Outcomes.

OBJECTIVES: To characterize the clinical, laboratory, histologic, molecular features, and outcome of gene-confirmed progressive familial intrahepatic cholestasis (PFIC) 1-3 among Arabs and to evaluate for "genotype-phenotype" correlations. STUDY DESIGN: We retrospectively reviewed charts of 65 children (ATP8B1 defect = 5, ABCB11 = 35, ABCB4 = 25) who presented between 2008 and 2019 with cholestasis. The clinical phenotype of a disease was categorized based on response of cholestasis and itching to ursodeoxycholic acid and ultimate outcome, into mild (complete response), intermediate (partial response, nonprogressive), and severe (progression to end-stage liver disease). RESULTS: Overall, 27 different mutations were identified (ATP8B1, n = 5; ABCB11, n = 11; ABCB4, n = 11), comprising 10 novel ones. Six patients with heterozygous missense mutations (ATP8B1, n = 2; ABCB11, n = 4) had transient cholestasis. Of the remaining 3 patients with PFIC1, 2 developed severe phenotype (splicing and frameshift mutations). Of the remaining 31 patients with PFIC2, 25 developed severe disease (15 due to frameshift and splicing mutations). Of 25 patients with PFIC3, 10 developed a severe phenotype (1 splicing and 3 frameshift mutations; 6 missense). Patients with PFIC2 had significantly shorter survival time and more rapid disease progression than patients with PFIC3 (P < .001). Patients with frameshift mutations in ABCB11 gene (p.Thr127Hisfs∗6) and ABCB4 gene (p.Phe210Serfs∗5) had significantly shorter survival time than missense mutations (P = .011; P = .0039, respectively). CONCLUSIONS: We identified genotype-phenotype correlations among mutations in ABCB11 and ABCB4 genes, which underscore the prognostic value of early genetic diagnosis. The disease course in patients with PFIC3 could be favorably modified by ursodeoxycholic acid therapy.

Clinical Characteristics, Laboratory Findings, Management, and Outcome of Severe Coronavirus Disease 2019 in Children at a Tertiary Care Center in Riyadh, Saudi Arabia: A Retrospective Study.

Background: Numerous studies worldwide have reported COVID-19 in children; however, the clinical symptoms and consequences of COVID-19 in children have only been reported in a few studies in Saudi and gulf region. Therefore, we aimed to investigate the clinical features and outcomes of COVID-19 infection in children and the therapeutic interventions used. Methods: This retrospective cohort study included 96 patients with confirmed severe acute respiratory syndrome coronavirus 2 infection aged ≤14 years who were admitted to a tertiary governmental care hospital in Riyadh, Saudi Arabia between March 2020 and November 2020. Data on children with COVID-19, including demographics, comorbidities, symptoms, imaging and laboratory results, therapies, and clinical outcomes, were analyzed. Results: Of 96 children admitted with a confirmed diagnosis of COVID-19, 63.8% were aged ≤ 3 years, 52.1% were male, 56.2% had an unknown source of infection, and 51% had no comorbidities. Most cases had severe infection (71.88%) as they required oxygen, 10.42% of whom were critical. The most common symptoms were respiratory-related (98%), and the common physical sign was fever (49%). High D-dimer (90.7%) and C-reactive protein (72.09%) levels were found in most cases. Oxygen (71.88%) was the most commonly used treatment. Most patients were discharged home and fully recovered (97.92%). We reported two deaths (2.08%). Conclusions: Our findings showed that the majority of the admitted children with COVID-19 were ≤3 years of age (52.1%) and infected with an unknown source (56.2%). Moreover, the majority of the cases had severe COVID-19 infection as they required oxygen (71.88%), although they had favorable outcomes. However, some cases were critical and resulted in death. Future studies will be crucial to better understand the disease spectrum and potential therapeutic options for COVID-19 in children.