Case Report: Pseudomonas liver abscess in a previously healthy child with homozygous pathogenic S allele variant of the SERPINA1 gene
Background Pyogenic liver abscess is an uncommon pediatric condition, and Pseudomonas aeruginosa represents a rare causative agent in otherwise healthy children. Such infections may signal an underlying inborn error of immunity. Alpha-1 antitrypsin (A1AT), encoded by the SERPINA1 gene, is a serine protease inhibitor with key immunomodulatory functions. In mouse models, A1AT prevents degradation of the antimicrobial SPLUNC1 protein to enhance host defense against Pseudomonas aeruginosa . In humans, while A1AT variants can be associated with a generally increased risk of respiratory infection, to our knowledge no corresponding impact with respect to P. aeruginosa has been reported. Case Description We report a previously healthy 14-month-old girl who developed P. aeruginosa liver abscess without identifiable predisposing factors. Comprehensive immunologic evaluation was unremarkable except for whole exome sequencing revealing homozygous S allele pathogenic SERPINA1 variant (c.863 A>T, p.E288V) known as the S allele associated with partial A1AT deficiency. The clinical presentation, microbiologic findings, and disease course suggested that defective A1AT function may have contributed to dysregulated inflammation and susceptibility to infection. Conclusion This case highlights a potential association between homozygosity in the pathogenic S variant of SERPINA1 and susceptibility to severe P. aeruginosa infection , in this case liver abscess. While A1AT deficiency is classically associated with pulmonary and hepatic disease, the immunomodulatory role of A1AT suggests broader relevance in host defense. Early recognition of underlying SERPINA1 defects in children with unusual or severe infections may inform prognosis, guide management, and prompt appropriate genetic counseling and surveillance for long-term complications.
Authors
- Alaric W. D’Souza (ORCID: https://orcid.org/0000-0002-8744-8136)
- Craig D. Platt (ORCID: https://orcid.org/0000-0002-1901-4563)
- Ofer Levy (ORCID: https://orcid.org/0000-0002-5859-1945)
- Sanya J. Thomas (ORCID: https://orcid.org/0000-0003-1607-9537)
- Musaab Alhezam
Institutions
- Broad Institute (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Precision Research (United States) (US)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2026-03-27
- DOI
- https://doi.org/10.3389/fimmu.2026.1755963
- Primary Topic
- Infections and bacterial resistance
- Type
- article
- Field-Weighted Citation Impact
- 0.00