Clinical Report: Identification of a new compound heterozygous variant in the NBAS gene

Overview

This report identifies novel compound heterozygous variants in the NBAS gene associated with hemophagocytic lymphohistiocytosis (HLH) and multisystem manifestations in a pediatric patient. The findings expand the clinical spectrum of NBAS-related diseases and highlight the potential for severe immune dysregulation.

Background

Biallelic variants in the NBAS gene are linked to various syndromic conditions, including infantile liver failure syndrome type 2 (ILFS-2) and short stature. Recent observations suggest that HLH may occur in patients with NBAS deficiency, indicating a severe inflammatory complication that can lead to rapid clinical deterioration. Understanding these associations is crucial for timely diagnosis and intervention.

Data Highlights

Novel compound heterozygous variants identified: c.5139-5T>G and c.5983C>T. The c.5983C>T variant is classified as likely pathogenic. The patient exhibited progressive cytopenias leading to pancytopenia and HLH.

Key Findings

• Identification of two novel compound heterozygous variants in the NBAS gene.
• Patient developed recurrent infections, short stature, and progressive cytopenias.
• HLH was observed as a severe complication in the context of NBAS deficiency.
• Functional studies indicated impaired NBAS function due to the identified variants.
• Systematic review of 322 patients provided insights into genotype–phenotype correlations.

Clinical Implications

The identification of HLH in patients with NBAS variants emphasizes the need for heightened awareness among clinicians. Early recognition of severe immune dysregulation can facilitate timely intervention and potentially improve outcomes.

Conclusion

This study expands the phenotypic spectrum of NBAS-related diseases and underscores the importance of recognizing HLH as a potential manifestation. Further research is needed to clarify the mechanisms underlying these associations.

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10. Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency - PMC