What is Familial Hemophagocytic Lymphohistiocytosis, PRF1-related? Familial hemophagocytic lymphohistiocytosis (fHLH) is a group of disorders that cause the immune system to be too active which leads to uncontrolled inflammation. Several genes are associated with fHLH. Familial hemophagocytic lymphohistiocytosis, PRF1-related, also known as FHL2, is caused by harmful genetic changes (variants) in the PRF1 gene. This gene is important for regulating the immune system. The first symptoms usually include high fever and infections, enlarged liver and spleen (hepatomegaly), and low blood cell counts (cytopenia). As the disease progresses, neurological symptoms may develop, including seizures, muscle problems, loss of the ability to move parts of the body (paralysis), and blindness. If left untreated, organ dysfunction and organ failure can occur. Individuals with this condition also have an increased risk of developing cancer, such as leukemia and lymphoma. Although severe symptoms often happen in the first few weeks or months of life, some individuals may experience symptoms later on. Most individuals with FHL2 have two harmful changes in the PRF1 gene. However, a few cases reported had one harmful change in the PRF1 gene and one in another gene associated with familial hemophagocytic lymphohistiocytosis (digenic inheritance). How common is Familial Hemophagocytic Lymphohistiocytosis, PRF1-related? Familial hemophagocytic lymphohistiocytosis has an incidence of 1 in 50,000 births. Harmful genetic changes in several genes cause the condition; approximately 30%-40% of cases are caused by harmful changes in the PRF1 gene. How is Familial Hemophagocytic Lymphohistiocytosis, PRF1-related, treated? Familial hemophagocytic lymphohistiocytosis can be cured by replacing the cells of the immune system with healthy ones from a donor, known as an allogeneic hematopoietic stem cell transplantation (HSCT). Patients also often require medicines to treat infections, such as antibiotics or antivirals. Some patients may need a blood transfusion. Individuals with FHL2 are best cared for through a medical team, including specialists in hematology, immunology, infectious disease, rheumatology, stem cell transplantation, neurology, and medical genetics. What is the prognosis for an individual with Familial Hemophagocytic Lymphohistiocytosis, PRF1-related? The prognosis for individuals with FHL2 can vary depending on several factors, including the severity of the disease at the time of diagnosis, the age of onset, treatment response, and the availability of a stem cell donor. Without treatment, individuals with FHL2 survive a few months after the onset of symptoms. Allogeneic stem cell transplantation improves survival. Other names forfamilial hemophagocytic lymphohistiocytosis, PRF1-related Hemophagocytic lymphohistiocytosis, familial 2 PRF1-related fHLH (PRF1-fHLH) familial HLH type 2 familial type 2 hemophagocytic lymphohistiocytosis References Almalky et al., 2020, Pan Afr Med J, 36:354, PMID 33224420 Canna et al., 2020, Blood, 135(16): 1332-1343, PMID: 32107531 Gregg et al., 2021, Genet Med., 23(10):1793-1806, PMID: 34285390 Ishii, 2016, Front Pediatr, 4:47, PMID: 27242976 Online Mendelian Inheritance in Man, OMIM [170280], 2023, https://omim.org/entry/170280 Shabrish et al., 2021, Front Immunol, 12, PMID: 33746956 Zhang et al., 2021, https://www.ncbi.nlm.nih.gov/books/NBK1444/