BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL) is a primary 
immunodefici-ency disease caused by gene defects. The onset of FHL in 
adolescents and adults may lead clinicians to ignore or even misdiagnose the 
disease. To the best of our knowledge, this is the first report to detail the 
clinical features of type 2 FHL (FHL2) with compound heterozygous perforin 
(PRF1) defects involving the c.163C>T mutation, in addition to correlation 
analysis and a literature review.
CASE SUMMARY: We report a case of a 27-year-old male patient with FHL2, who was 
admitted with a persistent fever and pancytopenia. Through next-generation 
sequencing technology of hemophagocytic lymphohistiocytosis (HLH)-related genes, 
we found compound heterozygous mutations of PRF1: c.65delC (p.Pro22Argfs*29) 
(frameshift mutation, paternal) and c.163C>T (p.Arg55Cys) (missense mutation, 
maternal). Although he did not receive hematopoietic stem cell transplantation, 
the patient achieved complete remission after receiving HLH-2004 treatment 
protocol. To date, the patient has stopped taking drugs for 15 mo, is in a 
stable condition, and is under follow-up observation.
CONCLUSION: The delayed onset of FHL2 may be related to the PRF1 mutation type, 
pathogenic variation pattern, triggering factors, and the temperature 
sensitivity of some PRF1 mutations. For individual, the detailed reason for the 
delay in the onset of FHL warrants further investigation.