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)

Hepatosplenic gamma/delta T-cell lymphoma is recognized as a subset of peripheral T-cell lymphoma in the REAL classification. Histologically these tumors are characterized by a mixture of small to medium-sized atypical lymphocytes. To date, approximately 15 cases of hepatosplenic gamma delta T-cell lymphoma have been reported. Affected individuals are usually young adults with a median age of 34 years. Patients commonly present with B symptoms and hepatosplenomegaly, but an absence of lymphadenopathy. The disease follows an aggressive course with median survival of 12-14 months and poor response to combination chemotherapy agents. Occasionally, the occurrence of frank blast transformation constitutes a terminal event for the patient. Although cytopenias are relatively common, nonimmune hemolytic anemia has been reported in one patient only. This is the first report of autoimmune hemolytic anemia associated with hepatosplenic gamma delta T-cell lymphoma.
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PMID:Gamma/delta T-cell hepatosplenic lymphoma: review of the literature, diagnosis by flow cytometry and concomitant autoimmune hemolytic anemia. 1706 Nov 1

Multicentric angiofollicular lymphnode hyperplasia (multicentric Castleman's disease) may be associated with acute phase reaction and several autoimmune features. Since lymphadenopathy is a common feature in connective tissue disease, a clear distinction between the different disease entities may be difficult. We describe a 26-year-old male patient with predominant cervical lymphadenopathy, hepatosplenomegaly and polyserositis, diagnosed as collagen disease. He showed several autoimmune features including autoimmune haemolytic anaemia, cryoglobulinaemia, positive antinuclear and anti smooth muscle antibodies, serum immune complexes and a sensorimotor polyneuropathy. Under immunosuppressive therapy with prednisolone and azathioprine, only partial remission was achieved. Repeated lymph node biopsy together with the clinical features led to the diagnosis of multicentric Castleman's disease in this patient nine years later. Interleukin-6 (IL-6) seems to play an important role in the pathogenesis of clinical and serum biochemical features in patients with Castleman's disease.
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PMID:Autoimmune findings resembling connective tissue disease in a patient with Castleman's disease. 913 32

Jaundiced mice, ja/ja, suffer from a severe hemolytic anemia caused by a complete deficiency of erythroid beta-spectrin. We used these mice as a model to investigate the pathophysiological consequences of the deficiency, including the effects in the nonerythroid tissues where this protein is expressed. Because the ja/ja mice rarely survive beyond the fourth postnatal day, methods were assessed for extending lifespan into adulthood. Neonatal transfusion increased lifespan to a mean of 3.7 months, allowing a more complete characterization of the pathophysiology. Blood parameters and histopathology of the jaundiced mouse were compared with that from spherocytic mice, which have a hemolytic anemia caused by deficiency of erythroid alpha-spectrin, yet can survive the postnatal period transfusion free. The adult jaundiced and spherocytic mice present with greatly decreased hematocrit and red blood cell counts, reticulocytosis, and bilirubinemia, leading secondarily to hepatosplenomegaly and cardiomegaly. Jaundiced and spherocytic mice were analyzed histopathologically between 1.0 and 9.5 months of age. Interestingly, the complete absence of erythroid beta-spectrin in jaundiced mice leads to no detectable structural defects in brain, cardiac, or skeletal muscles. However, fibrotic lesions and lymphocytic infiltration were observed in cardiac tissue from 4 of 13 jaundiced mice and 15 of 15 spherocytic mice, and thrombi were detected at either the atrioventricular valves or within the atria of 2 of 13 jaundiced mice and 15 of 15 spherocytic mice. In addition, all affected mice had a progressive renal hemosiderosis concurrent with hydronephrosis and glomerulonephritis. The severity of the renal disease and its presence in all moribund mice suggests kidney failure rather than the fibrotic heart lesions as the major cause of death in these mice.
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PMID:Thrombosis and secondary hemochromatosis play major roles in the pathogenesis of jaundiced and spherocytic mice, murine models for hereditary spherocytosis. 937 73

Porphyrias, a group of inborn errors of heme synthesis, are classified as hepatic or erythropoietic according to clinical data and the main site of expression of the specific enzymatic defect. Hereditary coproporphyria (HC) is an acute hepatic porphyria with autosomal dominant inheritance caused by deficient activity of coproporphyrinogen III oxidase (COX). Typical clinical manifestations of the disease are acute attacks of neurological dysfunction; skin photosensitivity may also be present. We report a variant form of HC characterized by a unifying syndrome in which hematologic disorders predominate: harderoporphyria. Harderoporphyric patients exhibit jaundice, severe chronic hemolytic anemia of early onset associated with hepatosplenomegaly, and skin photosensitivity. Neither abdominal pain nor neuropsychiatric symptoms are observed. COX activity is markedly decreased. In a first harderoporphyric family, with three affected siblings, a homozygous K404E mutation has been previously characterized. In the present study, molecular investigations in a second family with neonatal hemolytic anemia and harderoporphyria revealed two heterozygous point mutations in the COX gene. One allele bore the missense mutation K404E previously described. The second allele bore an A-->G transition at the third position of the donor splice site in intron 6. This new COX gene mutation resulted in exon 6 skipping and the absence of functional protein production. In contrast with other COX gene defects that produce the classical hepatic porphyria presentation, our data suggest that the K404E substitution (either in the homozygous or compound heterozygous state associated with a mutation leading to the absence of functional mRNA or protein) is responsible for the specific hematologic clinical manifestations of harderoporphyria.
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PMID:Neonatal hemolytic anemia due to inherited harderoporphyria: clinical characteristics and molecular basis. 945 77

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever, hepatosplenomegaly, hemolytic anemia, and polyclonal hypergammaglobulinemia. Morphologically, the involved lymph nodes demonstrate complete effacement of the normal architecture, prominent neovascularization and infiltration by immunoblasts and plasma cells. Other terms that have been used to describe this entity include diffuse plasmacytic sarcomatosis, immunoblastic lymphadenopathy, lymphogranulomatosis X, and immunologic aberrations in idiopathic reticulosis. Initially, AILD was thought to be a disease of B-cell origin that represented reactive immune response to unknown stimulus and high potential for malignant transformation. It is now evident that AILD in 80% of cases follows an aggressive course with short median survival, especially, if complete response with chemotherapy is not achieved. Immunologic and molecular studies have demonstrated that the majority of AILD cases are T-cell clonal disorders. Despite the numerous reports on the role of Epstein-Barr virus in this disorder, it is unknown whether the presence of this virus is associated with the immune defect that accompanies AILD, or whether it is a pathogenetic factor. In contrast to non-Hodgkin's lymphomas, a stage is not usually assigned to the patient since the disease is systemic in nature, subsequently, parameters such as extent of disease and tumor bulk used to identify high-risk patients with non-Hodgkin's lymphomas, do not appear to correlate with disease activity or prognosis in AILD. Treatment of AILD has been unsatisfactory, with approximately 25% of patients achieving complete and sustained remission when combined chemotherapy agents are used. This article is devoted to a discussion of the different manifestations, suggested pathogenesis, and treatment of AILD.
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PMID:Angioimmunoblastic lymphadenopathy with dysproteinemia: emphasis on pathogenesis and treatment. 985 98

In the gamma-glutamyl cycle, hereditary defects have been described in four of the six enzymes namely: gamma-GC synthetase; GSH synthetase; gamma-glutamyl transpeptidase and 5-oxoprolinase. Mutants are still to be found in gamma-glutamyl cyclotransferase and in the dipeptidase. Deficiency of GSH synthatase or gamma-GC synthetases results in low levels of GSH. In gamma-GC synthetase deficiency hemolytic anemia is the most prominent symptom, with or without hepatosplenomegaly. In generalized GSH synthetase deficiency 5-oxoproline is overproduced due to lack of feedback inhibition of gamma-GC synthetase. These patients have metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and about 50% of them also have progressive neurological symptoms. Treatment includes acidosis correction, high doses of vitamin E and C and avoidance of drugs precipitating hemolytic crises in G6PD deficiency. Therapeutic trials with GSH analogues, N-acetylcysteine and GSH esters have been carried out. Glutathione synthetase deficiency restricted to erythrocytes results in hemolytic anemia but no 5-oxoprolinuria. gamma-Glutamyl transpeptidase deficiency is associated with GSH-emia and GSH-uria whereas 5-oxoprolinase deficiency is associated with 5-oxoprolinuria. In diagnostic work it must be emphasized that erythrocytes contain an incomplete gamma-glutamyl cycle; they lack both gamma-glutamyl transpeptidase and 5-oxoprolinase and these enzyme activities must therefore be analyzed in other types of cells such as leukocytes and fibroblasts. It is also important to investigate other patients with inherited defects in the gamma-glutamyl cycle to learn more about the biological role of GSH in man.
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PMID:Patients with genetic defects in the gamma-glutamyl cycle. 967 48

Eight patients who were carriers of beta-thalassemia induced by the cd121 (G-->T) mutation are described in four nonrelated Dutch families. This mutant, which is considered rare and inherited in a dominant manner, is expressed in a different way among each of the four families and even among carriers of the same family. The symptoms vary from an hemolytic anemia of intermediate gravity with hepatosplenomegaly, inclusion bodies and erythroblastosis, to a mild anemia with minor hematological abnormalities. We report the analytical procedures used for the detection of the mutant, the hematological and clinical data of the four families and discuss the variable physiopathology of this molecular defect. We also compare the variation in fetal hemoglobin expression in relation to the haplotypes of the beta-gene cluster and to the different hematological conditions. The presence of this rare mutant in four nonrelated Dutch families could derive from a single mutation or from multiple events. The existence of the four mutations in three different haplotypes suggests the occurrence of at least two independent events. The presence of five abnormal hemoglobins and the beta-thalassemia defect on different haplotypes at cd121 also suggests a relatively increased rate of mutations at this particular site.
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PMID:Phenotype variability of the dominant beta-thalassemia induced in four Dutch families by the rare cd121 (G-->T) mutation. 987 60

This is a case of an infant boy born at 28 weeks gestational age who presented on the 42nd day of life with hepatosplenomegaly, haemolytic anaemia, thrombocytopenia and atypical lymphocytes on the peripheral blood smear. He had an Epstein Barr virus (EBV) viral capsid antigen (VCA) IgM antibody titre of 1:160 and a positive test for heterophil antibodies. The cytomegalovirus (CMV) IgM titre was 0.600 and CMV IgG 70 Au/ml. The infant died 10 d later and the autopsy showed CMV inclusion bodies in the lungs, liver and kidneys. EBV infection acquired perinatally, probably co-existing with CMV, may have led to a fatal disease.
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PMID:Perinatal Epstein Barr virus infection in a premature infant. 1038 Dec 27

Side effects such as cutaneous vasculitis, which occur during prolonged levamisole treatment, may discourage the utilization of the drug in relapsing nephrotic syndrome. We describe a child who developed disseminated vasculitis during prolonged treatment with levamisole. The acute phase was characterized by hepatosplenomegaly, hemolytic anemia, IgM anticardiolipin and p-antineutrophil cytoplasmic antibodies. One month after withdrawal of therapy all symptoms had disappeared and tests normalized. This case report, together with other reports on cutaneous vasculitis, suggest caution and close monitoring during prolonged levamisole therapy.
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PMID:Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome. 1097 25

A 9-month-old boy had bruising and petechiae. Investigation revealed a Coombs-positive hemolytic anemia and immune-mediated thrombocytopenia. The infant was treated with intravenous immunoglobulin and steroids. The infant eventually had recurrent fevers, hepatosplenomegaly, pulmonary nodules, and parenchymal central nervous system (CNS) lesions develop. Results of a lung biopsy revealed a polyclonal lymphoproliferative disease. Polymerase chain reaction analysis showed the presence of the Epstein-Barr (EB) viral genome in the lung nodules. The infant died from progressive lung disease 6 months after the initial symptoms of Evans syndrome. Lymphoproliferative disease is known to occur in a variety of settings after immunosuppression, especially in solid organ transplant recipients. We report a case of polyclonal lymphocyte proliferation in a patient with Evans syndrome.
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PMID:Fatal lymphoproliferative disease as a complication of Evans syndrome. 1103 62


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