Application of detection of mutations in blood and immunodeficiency genes in the diagnosis of HLH patients

ABSTRACT To investigate the value of genetic mutations in the pathogenesis and differential diagnosis of hemophagocytic lymphohistiocytosis (HLH), the mutations related to blood and immune deficiency genes were analyzed in patients with HLH. Peripheral blood samples from 33 children diagnosed with HLH according to the 2004 diagnostic criteria were collected, and 317 gens related with blood system diseases and 562 genes related with immunodeficiency were detected by the second generation targeted sequencing technology, bioinformatic analysis and parental verification analysis. A total of 159 mutations related with blood system diseases and immunodeficiency were found in 33 patients, including 7 HLH-related gene mutations (UNC13D, XIAP, LYST, STX11, ITK, PRF1 and SRGN) in 12 patients. UNC13D was found in 6 patients, with the highest frequency. Two cases (6.1%, 2/33) were diagnosed as primary hemophagocytic lymphohistiocytosis (pHLH), and six cases (18.2%, 6/33) were diagnosed as primary immunodeficiency disease (PID) or hereditary hematopathy, and the others were diagnosed as secondary hemophagocytic lymphohistiocytosis (sHLH). It is necessary to detect blood and immunodeficiency genes to exclude the possibility of pHLH, PID or hereditary hematopathy associated with HLH for children.