Screening of familial hemophagocytic lymphohistiocytosis in neonatal sepsis

Objective: In order to investigate whether the diagnosis of hemophagocytic lymphohistiocytosis (HLH) in newborns with sepsis may be overlooked, it was aimed to investigate the presence of genetic mutations associated with primary HLH in patients who meet the specified criteria, since sepsis and primary HLH in the neonatal period show similar clinical and laboratory findings. Materials and Methods: In 22 newborn patients who were followed up with the diagnosis of sepsis in the Neonatal Intensive Care Unit of Karadeniz Technical University Faculty of Medicine, Department of Pediatrics, between July 2019 and June 2021, and fulfilled at least 2 of the 3 criteria for 1)History of consanguineous marriage or sibling death, 2)Hepatosplenomegaly 3)Hyperferritinemia(>500 ng/mL), genetic mutations associated with familial HLH were screened. Results: In our study, homozygous or heterozygous polymorphisms of c.1576A>G (I526V) in the STXBP2 gene and c.2599G>A (K867E) in the UNC13D gene were detected in 12 patients, classified in the "benign" category in the literature. Heterozygous mutation was demonstrated in 6 patients; c.1034C>T (T345M) in STXBP2 gene in 2 patients, one patient each had heterozygous mutations of c.1470G>A (R490Q) in the STXBP2 gene, c.799G>A (V267M) in the STX11 gene, c.1759G>A (R587C) in the UNC13D gene, c.1620A>G (p.Gln540=) in the PRF1 gene detected. Two of the patients with heterozygous mutations had polymorphisms associated with HLH. Polymorphism associated with HLH clinic was detected in 3 patients without mutation; c.272C>T (A91V) heterozygous polymorphism in PRF1 gene was found in 1 patient and c.175G>A (A59T) heterozygous polymorphism in UNC13D gene in 2 patients. Conclusion: Heterozygous mutations or polymorphisms in genes associated with HLH were detected in newborn patients diagnosed with sepsis and meeting the specified criteria. As cases of HLH with these mutations or polymorphisms have been reported in the literature, we recommend further investigation of HLH in newborn diagnosed with sepsis with at least 2 of these criteria. Key words: Sepsis, hemophagocytic lymphohistiocytosis, mutation