Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) mutation and EBV-associated T-cell lymphoproliferative disorder of the thyroid

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%­50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein­Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.

Novel STXBP2 Mutation Causing Familial Hemophagocytic Lymphohistiocytosis.

Familial Hemophagocytic Lymphohistiocytosis (FHL) is a rare autosomal recessive disorder. Diagnosis is established in presence of genetic mutation or positive family history in one of the siblings. Common genetic mutations associated with FHL are mutations in gene PRF-1 (also known as FHL 2), UNC13D (FHL 3) and STX11 (FHL 4). Recently mutation in STXBP2 encoding syntaxin binding protein 2 (Munc 18 -2) has been found to be associated with FHL type 5. Here we describe the first reported Indian patient with homozygous mutation in STX BP2 gene (c1697 G>A resulting in amino acid change p.G566D) causing FHL 5.

Prolonged Remission Following Autologous Peripheral Blood Stem Cell Transplantation in an Infant with Familial Hemophagocytic Lymphohistiocytosis / 대한혈액학회지

Familial hemophagocytic lymphohistiocytosis (FHL) is a fatal illness with a median life expectancy of 2 months if not treated. However, with the recent employment of allogeneic bone marrow transplantation in the treatment of FHL, even complete cure might be anticipated. We report here a case of prolonged remission following autologous peripheral blood stem cell transplantation (Auto-PBSCT) which was first attempted for FHL in Korea. A 4-month-old girl presented with high fever and a huge hepatosplenomegaly. Bone marrow examination revealed the proliferation of both non-malignant histiocytes engulfing red blood cells and lymphocytes. Her brother died at the age of 18 months showing quite similar manifestations. A diagnosis of FHL was made. Following 8 courses of chemotherapy with multiple drugs, Auto-PBSCT was performed. She has been well without any evidence of disease over 8 months of post- transplant period. This case illustrates that it might be worth trying Auto- PBSCT in the treatment of FHL.

EBV-elicited familial hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is a rapidly fatal illness, usually encountered in infancy, characterized by fever, hepatosplenomegaly, pancytopenia, and central nervous system involvement. Microscopic examination of tissue shows a non-malignant lymphohistiocytic infiltrate, with prominent erythrophagocytosis. FHL is an autosomal recessive hereditary disorder but may develop secondarily to other conditions such as immunosuppression, malignancies, fat overload and certain infections. We recently experienced a case of siblings developing FHL, which may be associated with EBV infection.