Resolution of recurrent pediatric acute liver failure with liver transplantation in a patient with NBAS mutation

• Type of Material: Article
• Authors: Dellys Soler Rodriguez, Emory University; Duke Geem, Emory University; Wenxiao Jiang, Otogenetics Corporation; Heather Rytting, Emory University; Shanmuganathan Chandrakasan, Emory University; Anand Salem, Emory University; James P Stevens, Emory University; Saul Karpen, Emory University; Joseph Magliocca, Emory University; Rene Romero, Emory University; Dellys Soler Rodriguez, Emory University
• Language: English
• Date: 2021-07-20
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Wiley Periodicals LLC
• Final Published Version (URL): http://dx.doi.org/10.1111/petr.14084
• Title of Journal or Parent Work: PEDIATRIC TRANSPLANTATION
• Volume: 25
• Issue: 7
• Start Page: e14084
• End Page: e14084
• Grant/Funding Information: The project described was supported by Award Number T32DK108735 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.
• Keywords: liver transplantation; pediatric liver; GENE; CHILDREN; Science & Technology; pediatric; Life Sciences & Biomedicine; immunocompromised host; ONSET; acute liver failure; NBAS; Transplantation; transplantation; Pediatrics

Abstract

Background: Pediatric acute liver failure (PALF) remains an enigmatic process of rapid end-organ dysfunction associated with a variety of pathologic conditions though the predominant cause is indeterminate. A growing body of research has identified mutations in the NBAS gene to be associated with recurrent acute liver failure and multi-systemic disease including short stature, skeletal dysplasia, facial dysmorphism, immunologic abnormalities, and Pelger-Huët anomaly. Methods and Results: Here, we describe a 4-year-old girl who presented with dehydration in the setting of acute gastroenteritis and fever but went on to develop PALF on day 2 of hospitalization. She clinically recovered with supportive measures, but after discharge, had at least 2 additional episodes of PALF. Ultimately, she underwent liver transplant and her recurrent episodes of PALF did not recur throughout a 6-year follow-up period. Whole-exome sequencing post-liver transplant initially revealed two variants of uncertain significance in the NBAS gene. Parental studies confirmed the c.1549C > T(p.R517C; now likely pathogenic) variant from her mother and a novel c.4646T > C(p.L1549P) variant from her father. In silico analyses predicted these variants to have a deleterious effect on protein function. Consistent with previously characterized NBAS mutation-associated disease (NMAD), our patient demonstrated the following features: progeroid facial features, hypoplasia of the 12th ribs, Pelger-Huët anomaly on peripheral blood smear, and abnormal B and NK cell function. Conclusion: Altogether, we describe a novel pathogenic variant in the NBAS gene of a patient with NMAD and report the resolution of recurrent PALF secondary to NMAD following liver transplantation.