Hemophagocytic lymphohistiocytosis is a multisystem inflammation, generated by 
the uncontrolled and excessive activation of cytotoxic T lymphocytes and natural 
killer cells. Severe immunodeficiency and generalized macrophage activation can 
often be detected in the background of this life threatening disorder. It is 
classified as a primary immunodeficiency. Functional abnormalities of the 
perforin protein or defects in granule secretory mechanisms are caused by gene 
mutations in most cases. Diagnostic criteria of hemophagocytic 
lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting 
at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and 
hyperferritinemia, elevated serum level of soluble interleukin-2 receptor 
(sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased 
cytotoxic T cell and natural killer cell activity. In this case report the 
authors summarize the utility of functional flow cytometry in the diagnosis of 
hemophagocytic lymphohistiocytosis. Using flow cytometry, elevated intracellular 
perforin content, decreased killing activity of cytotoxic T cells and natural 
killer cells, and impaired cell surface expression of CD107a (LAMP1 protein) 
from in vitro stimulated blood lymphocytes were detected. Abnormal secretion of 
perforin was also demonstrated. Genetic testing revealed mutation of the MUNC 
13-4 gene, which confirmed the base of the abnormal flow cytometric findings. 
This case report demonstrates the value of functional flow cytometry in the 
rapid diagnosis of genetically determined hemophagocytic lymphohistiocytosis, a 
condition in which early diagnosis is critical for optimal management. The 
authors emphasize the significance of functional flow cytometry in the 
differential diagnosis of immunodeficiencies.