Familial Hemophagocytic Lymphohistiocytosis Screening in Neonatal Sepsis.

Objective: Neonatal sepsis and familial hemophagocytic lymphohistiocytosis (fHLH) have similar clinical and laboratory symptoms and the possibility of overlooking fHLH diagnosis is high in newborns with sepsis. History of consanguineous marriage and/or sibling death, hepatomegaly/splenomegaly, and hyperferritinemia (>500 ng/mL) are likely to support fHLH in newborns with sepsis. Therefore, in newborns with sepsis in whom at least 2 of these 3 criteria were detected, genetic variants was investigated for the definitive diagnosed of fHLH. According to the results of genetic examination, we investigated whether these criteria supporting fHLH could be used as a screening test in fHLH.

Materials and methods: fHLH-associated genetic variants were investigated in 22 patients diagnosed with neonatal sepsis who fulfilled at least 2 of the following criteria (1) history of consanguineous marriage and/or sibling death, (2) hepatomegaly/splenomegaly, and (3) hyperferritinemia (>500 ng/mL).

Results: Heterozygous variants were determined in 6 patients (27.2%): 3 STXBP2 , 1 STX11 , 1 UNC13D , and 1 PRF1 . Polymorphisms associated with the clinical symptoms and signs of HLH were determined in 5 patients (22.7%): 4 UNC13D , 1 PRF1 . Two patients were in the heterozygous variants and polymorphism associated with the clinical symptoms and signs of HLH groups. In 12 patients, benign polymorphisms were detected in STXBP2 and UNC13D genes. No change in fHLH associated genes were found in 1 patient.

Conclusion: Some variants and/or polymorphisms identified in our patients have been previously reported in patients with HLH. Therefore, we recommend further investigation of fHLH in patients with neonatal sepsis who fulfill at least 2 of the above 3 criteria.