AUTHOR=Fazi C. , Lodi L. , Magi L. , Canessa C. , Giovannini M. , Pelosi C. , Pochiero F. , Procopio E. , Donati M. A. , Azzari C. , Ricci S. 

TITLE=Case Report: Zellweger Syndrome and Humoral Immunodeficiency: The Relevance of Newborn Screening for Primary Immunodeficiency

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.852943

DOI=10.3389/fped.2022.852943

ISSN=2296-2360

ABSTRACT=Background: Zellweger Syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities and multi-organ damage, due to intracellular accumulation of very long chain fatty acids (VLCFAs).
Case presentation: We report the case of an infant affected by Zellweger Syndrome in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through New Generation Sequencing (NGS), which had previously confirmed the diagnostic suspicion of Zellweger Syndrome, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected.   
Conclusion: In this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-kB) pathway, which is crucial for B cells survival, with this work we hypothesize the existence of a link between Zellweger Syndrome and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.