1. Resolution of recurrent pediatric acute liver failure with liver transplantation in a patient with NBAS mutation.
- Author
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Geem, Duke, Jiang, Wenxiao, Rytting, Heather B., Chandrakasan, Shanmuganathan, Salem, Anand, Stevens, James P., Karpen, Saul J., Magliocca, Joseph F., Romero, Rene, and Rodriguez, Dellys Soler
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LIVER transplantation , *LIVER failure , *SKELETAL dysplasia , *SHORT stature , *KILLER cells , *DEHYDRATION , *CHILD patients , *GENETIC mutation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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