Hemophagocytic Lymphohistiocytosis in Association With Neuroblastoma Amplified Sequence (NBAS) Gene Variants: A Report of a Rare Case

• Published in: Curēus (Palo Alto, CA) Vol. 16; no. 9; p. e69690
• Main Authors: Gawhale, Siddhi, Tambolkar, Sampada, Tamhankar, Parag, Tandur, Balasubramanya S, Verma, Sarita
• Format: Journal Article
• Language: English
• Published: United States Cureus 19.09.2024
• Subjects: Genetics; Hematology; Pediatrics; immunomodulation; natural killer; stem cell applications; primary hlh; nbas gene mutation; hemophagocytic lymphohistiocytosis (hlh)
• ISSN: 2168-8184; 2168-8184
• DOI: 10.7759/cureus.69690

Hemophagocytic lymphohistiocytosis (HLH) is a multisystem involvement, hyperinflammatory state with rapid progression and a poor outcome. However, HLH may rarely present with signs and symptoms isolated to the central nervous system (CNS). Thus, we discuss this case, which presented with CNS symptoms and worsened over time with multisystem involvement, an inflammatory storm, and required immunomodulation. Whole exome sequencing performed on genomic DNA extracted from peripheral blood showed a novel finding that the patient was likely compound heterozygous for the following two novel variants of uncertain significance in the neuroblastoma amplified sequence (NBAS) gene (chr2:g.15461289C>T) or c.2251G>A (p.Asp751Asn) on Exon 21 and (chr2:g.15467334A>G) or c.2092T>C (p.Tyr698His) on Exon 19 (genomic coordinates in the GRCh37 format, transcript ID: NM_015909.4). The NBAS gene is needed for cytotoxic degranulation in natural killer (NK) cells and mutation of which dysregulates lytic vesicle transport, thus leading to the hyperinflammatory state. To the best of our knowledge and according to the available literature, this NBAS gene is a rarely documented cause of primary HLH.