Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial hemophagocytic lymphohistiocytosis (FHL) is, without treatment, an invariably fatal disease of infancy and early childhood characterized by fever, hepatosplenomegaly, pancytopenia, and a widespread accumulation of T-lymphocytes and macrophages. During recent years, the diagnosis and the survival as well as the understanding of the disease have improved dramatically. Recent studies suggest that FHL is caused by impaired lymphocyte-mediated cytotoxicity and defective triggering of apoptosis, and that the symptoms are mediated by a pro-inflammatory hypercytokinemia. Moreover, specific genetic alterations, mutations in the perforin gene, have been revealed in FHL patients. Perforin, which normally is secreted from cytotoxic T-lymphocytes and natural killer (NK) cells upon conjugation between effector and target cells, is able to insert into the membrane of the target cell. It there polymerizes to form a cell death-inducing pore through which toxic granzymes may enter the cell and trigger apoptosis. The establishment of perforin deficiency as a cause of the rapidly fatal disease FHL has demonstrated the essential role of perforin in human immune homeostasis.
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PMID:Biology and treatment of familial hemophagocytic lymphohistiocytosis: importance of perforin in lymphocyte-mediated cytotoxicity and triggering of apoptosis. 1197 53

Perforin is critical for cytotoxicity mediated by granules present in natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Perforin-deficient mice have impaired cytotoxicity by NK cells and CTLs, resulting in failure to control infections with certain viruses or bacteria. Infection of perforin-deficient mice with lymphocytic choriomeningitis virus results in haemophagocytic lymphohistiocytosis and elevated levels of pro-inflammatory cytokines. Mutations throughout the perforin gene have been identified in patients with familial haemophagocytic lymphohistiocytosis (FHL) type 2. These patients present with fever, hepatosplenomegaly, pancytopenia, have marked elevations of T-helper type 1 and type 2 cytokines, and have impaired NK cell and CTL cytotoxicity. A number of infectious pathogens have been implicated as triggering the onset of disease. Identification of mutations in perforin as the cause of FHL should allow prenatal diagnosis of the disorder. While stem cell transplantation is curative, gene therapy might be effective in the future.
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PMID:Perforin and lymphohistiocytic proliferative disorders. 1575 77

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive immune disorder, characterized by fever, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, markedly elevated levels of inflammatory cytokines, and impaired cytotoxic activity of lymphocytes. FHL is often fatal in early infancy. Histologic features include organ infiltration by activated macrophages and lymphocytes. Four genetic loci (FHL1, 2, 3, and 4) have been identified, of which FHL2 involves mutations in the perforin gene and is present in 20-50% of patients with FHL. We herein report the first comprehensive molecular analysis of 16 unrelated cases of FHL in ethnic Omanis. Using direct DNA sequencing analysis in 11 families, seven different mutations were identified in the coding region of the perforin gene, of which five were novel. Perforin gene defects do not seem to be involved in one-third of the cases of FHL in ethnic Omanis.
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PMID:Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic Omani patients. 1767 59

Hemophagocytic lymphohistiocytosis with central nervous system involvement is caused by inflammatory factor storms. The inflammatory factors invade the blood-brain barrier and further infiltrate brain tissue resulting in associated neurological and/or psychiatric symptoms in hemophagocytic lymphohistiocytosis with central nervous system involvement patients. This case report is based on a 14-year-old male patient who experienced intermittent dizziness and blurred vision about five years before admission as well as lower limb weakness and unstable walking approximately three years before admission. His brain MRI showed abnormal signals in the bilateral cerebellar hemisphere and vermis, right occipital lobe, and bilateral basal ganglia. The cerebrospinal fluid examination revealed an increase in nucleated cells, mainly monocytes, and elevated protein. He had no typical manifestation of hemophagocytic lymphohistiocytosis in the early stage, such as fever, cytopenia, or hepatosplenomegaly. He was misdiagnosed with meningoencephalitis or tuberculous meningitis. Perforin gene detection revealed a mutation in the PRF1 gene. The final diagnosis of type 2 familial hemophagocytic lymphohistiocytosis was made based on the neurological symptoms and genetic test. The possibility of hemophagocytic lymphohistiocytosis needs to be considered in patients with unexplained central nervous system symptoms, even if the patient does not have typical hemophagocytic lymphohistiocytosis symptoms, such as fever, cytopenia, or hepatosplenomegaly. We present the neurological symptoms of familial hemophagocytic lymphohistiocytosis type 2.
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PMID:Neurological symptoms of familial hemophagocytic lymphohistiocytosis type 2. 3225 94