Familial haemophagocytic lymphohistiocytosis (FHL) is an inherited disorder characterized by an impaired cytotoxicity of T lymphocytes and NK cells typically manifesting within first few months after birth. If not treated adequately, it is inevitably fatal within several months. The incidence in Caucasians has been estimated to 1: 50 000 births. Haematopoietic stem cell transplantation represents the only curative treatment for FHL. Recently, several genetic defects underlying molecular defects in FHL have been identified. In approximately 30% of patients FHL is caused by mutations in PRF1 gene coding for perforin. Further 30% of patients were found to have mutations in UNC13D coding for hMunc13-4 protein. Very recent report has identified another cause of FHL, mutations in STX11 gene on chromosome 6, coding for syntaxin 11. Absence of any of those proteins severely impairs the process of exocytosis of cytotoxic granules. We describe patient with clinical symptoms of FHL. Immunological and molecular biology methods led to the identification of perforin mutation as a cause of the disease. Patient received an allogeneic SCT from HLA-matched unrelated donor. SCT was followed by rapid normalization of clinical symptoms and laboratory findings. In patient described in this study, FHL manifested with typical clinical and laboratory symptoms. Adequate immunosuppressive treatment and subsequent SCT led to the sustained remission of FHL and correction of molecular defect. This is the first case of FHL in Czech Republic where perforin mutation was identified as a molecular cause both at cellular and molecular level.

        Key words: familial heamophagocytic lymphohistiocytosis, perforin, test of cytotoxicity, bone marrow transplantation, mixed chimerism.