Adult onset type 2 familial hemophagocytic lymphohistiocytosis with c.65delC/c.163C>T compound heterozygous mutations: A case report.

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 () 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 : 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 mutation type, pathogenic variation pattern, triggering factors, and the temperature sensitivity of some mutations. For individual, the detailed reason for the delay in the onset of FHL warrants further investigation.