Hepatology Commons^™

Impact Of Genetic And Non-Genetic Factors On Phenotypic Diversity In Nbas-Associated Disease, Nicole Hammann, Dominic Lenz, Ivo Baric, Ellen Crushell, Carlo Dionisi Vici, Felix Distelmaier, Francois Feillet, Peter Freisinger, Maja Hempel, Anna L. Khoreva, Martin W. Laass, Yves Lacassie, Elke Lainka, Catherine Larson-Nath, Zhongdie Li, Patryk Lipiński, Eberhard Lurz, André Mégarbané, Susana Nobre, Giorgia Olivieri, Bianca Peters, Paolo Prontera, Lea D. Schlieben, Christine M. Seroogy, Cristina Sobacchi, Shigeru Suzuki, Christel Tran, Jerry Vockley

School of Medicine Faculty Publications

Biallelic pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause a pleiotropic multisystem disorder. Three clinical subgroups have been defined correlating with the localisation of pathogenic variants in the NBAS gene; variants affecting the C-terminal region of NBAS result in SOPH syndrome (short stature, optic atrophy, Pelger-Huët anomaly), variants affecting the Sec 39 domain are associated with infantile liver failure syndrome type 2 (ILFS2) and variants affecting the ß-propeller domain give rise to a combined phenotype. However, there is still unexplained phenotypic diversity across the three subgroups, challenging the current concept of genotype-phenotype correlations in NBAS-associated disease. Therefore, besides examining the genetic …

Biochemical Testing For The Diagnosis Of Wilson's Disease: A Systematic Review, Hafiz Muhammad Salman, Mahwish Amin, Javaria Syed, Zouina Sarfraz, Azza Sarfraz, Muzna Sarfraz, Maria Jose Farfán Bajaña, Miguel Felix, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Background: Wilson's disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24-hour urinary copper, and ceruloplasmin using the Leipzig criteria.
Methods: Adhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along …

Ontogeny Related Changes In The Pediatric Liver Metabolome., Christopher M. Wilson, Qian Li, R Gaedigk, Chengpeng Bi, Saskia N. De Wildt, J Steven Leeder, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

Background: A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.

Methods: Metabolites …

Alternative Splicing Of The Slco1b1 Gene: An Exploratory Analysis Of Isoform Diversity In Pediatric Liver., Bianca D. Van Groen, Chengpeng Bi, Roger Gaedigk, Vincent S. Staggs, Dick Tibboel, Saskia N. De Wildt, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age-dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus-adolescents). Twenty-seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with …

All Ttg Positive Patient Do Not Have Celiac Disease, Pankaj Vohra, Kalyan Ray Parashette, Rajmohan Dharmaraj, Angela Deubel, Richardo Castillo, Jacqueline Fridge

Pediatrics Research and Scholarship

Tissue transglutaminase antibody IgA level (tTG) is an excellent screening test for celiac disease in the presence of adequate IgA levels. Most labs while screening for Celiac disease (CD) will do the IgA levels automatically. However the serological test is not a diagnostic test.

Cow's Milk Protein-Induced Villous Atrophy And Elevated Celiac Autoimmunity In Children With Celiac Disease On A Glutten-Free Diet: A Report Of Three Cases, Kristin Capone, Naire Sansotta, Pankaj Vohra, Stefano Guandalini

Pediatrics Research and Scholarship

Objective: To describe the serologic and histologic response of three patients with celiac disease who had persistent autoimmunity and villous atrophy despite a strict gluten-free diet, to the elimination of cow's milk protein.

Practice Survey: Adherence Monitoring And Intervention In Pediatric Gastroenterology And Hepatology., Michele H. Maddux, Shawna Ricks, Julie A. Bass, James F. Daniel, Ellen Carpenter, Kimberely Radford

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Despite significant medication nonadherence rates among youth with pediatric gastroenterology and hepatology disorders, little is known about current adherence practices in pediatric gastroenterology care. This study summarizes current practices surrounding adherence monitoring and intervention in pediatric gastrointestinal (GI) and hepatologic care in the USA.

Participants and methods: One hundred and fifty-four pediatric GI providers completed an online survey designed to examine current practices surrounding adherence monitoring and intervention, specific strategies used to monitor and treat poor adherence, and the barriers currently experienced in relation to adherence monitoring and intervention.

Results: Practices varied greatly in terms of when and how …