Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with Gaucher's disease who underwent partial splenectomy have been followed for 3, 7 3/4, and 8 1/2 years. All have had significant regrowth of the the splenic remnant and some recurrence of hypersplenism. A review of all previously reported cases also substantiates the recurrence of splenomegaly and hypersplenism. Among new options for the therapy of Gaucher's disease, enzyme replacement therapy (Ceredase) holds great promise for effective treatment.
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PMID:Subtotal splenectomy for Gaucher's disease: a follow-up study. 825 44

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047). The disease results from inherited defects of acid beta-glucosidase and the accumulation of the substrate, glucosylceramide, in cells of monocyte/macrophage origin. The therapeutic response to macrophage-targeted (alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every 2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15 splenectomized) with extensive Gaucher disease over periods of 6 to 24 months. The efficacy of several different doses and dosage reductions was evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n = 19), hemoglobin levels and platelet counts increased by 0% to 178% and 15% to 155%, respectively, within 3 to 12 months. In patients with splenomegaly (n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively. Hematologic and visceral improvements were noted at any doses between 60 and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic responses were persistent throughout therapy, with doses reduced by 50%. Pulmonary Gaucher disease did not improve clinically in 3 patients. Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1) did not influence the rate of patient improvement. Two of five patients who developed serum antibodies against alglucerase during the first 6 to 12 months of therapy had mild antibody reactions. This study shows similar regression of clinical Gaucher disease manifestations with enzyme therapy, using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was not diminished after 50% to 75% dose reductions or in the presence of anti-enzyme antibodies.
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PMID:Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months. 839 97

Gaucher disease (GD) is frequently associated with reduced plasma levels of low density lipoproteins, presumably due to increased catabolism of LDL. The purpose of this study was to determine the distribution of Tc-99m LDL (Tc-LDL) in Gaucher patients, and compare the findings to bone marrow distribution. Four patients with non-neuropathic Gaucher disease (type 1) underwent baseline whole body imaging at 4 and 24 h after injection of dialyzed autologous LDL labeled with 10-20 mCi Tc-99m-pertechnetate. Three of the four patients were treated with macrophage-targeted alglucerase (Ceredase). The LDL studies were compared to concurrent bone marrow scans performed with 10 mCi Tc-99m sulfur colloid (Tc-SC). Follow-up Tc-LDL and Tc-SC scans were obtained 12-14 months later. Tc-LDL activity was abnormally increased in the spleen and long bones of the upper and lower extremities. Liver activity was also increased. Prominent blood pool activity 4 h after injection mostly cleared on the 24-hour images. The distribution of Tc-SC was congruent with Tc-LDL activity. All patients had mild-to-moderate hepatomegaly and peripheral bone marrow expansion. One patient had been previously splenectomized and the remaining three had moderate-to-severe splenomegaly. Two of the three treated patients showed regression of peripheral bone marrow activity with therapy, along with a comparable decrease in Tc-LDL uptake. Our study with Tc-LDL and Tc-SC suggests that in patients with Gaucher disease native LDL is taken up by the reticuloendothelial system (RES) of the spleen and bone marrow in addition to increased uptake by the liver. This abnormal uptake (presumably by macrophages of the RES) may account for accelerated LDL catabolism and reduced plasma levels of LDL. Serial LDL studies can be performed, allowing for longitudinal follow-up after drug or enzyme therapies.
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PMID:Scintigraphic evaluation of Tc-99m-low-density lipoprotein (LDL) distribution in patients with Gaucher disease. 927 6

Imiglucerase, the recombinantly produced enzyme, is gradually replacing the human placental derived alglucerase in the treatment of gaucher patients. We describe the first case, to the best of our knowledge, of an anaphylactoid reaction to imiglucerase in a patient who tolerated alglucerase. The patient was diagnosed at the age of 2 4/12 years with anemia and hepatosplenomegaly. Over the years he had suffered from marked splenomegaly, thrombocytopenia and recurrent bleeding episodes. At the age of 24 he started treatment with imiglucerase. After 3 months of treatment, immediately after starting an infusion, he experienced flushing, cough, tachycardia, palpitation, chest pain and excessive sweating, which reoccurred on a consecutive administration. Substitution with alglucerase was tolerated well, with only mild rash when he was premedicated with benadryl. Immediate skin tests to alglucerase, imiglucerase and gelatin were negative. IgG against alglucerase was undetectable. The in vitro mast cell degranulation test was positive for alglucerase, imiglucerase heamaccel (a gelatin based plasma substitute, which is a component of imiglucerase). This sensitivity to imiglucerase but not to alglucerase, raises the question of future treatment for this patient, since the production of alglucerase may cease, once imiglucerase production will cover the need for replacement enzyme.
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PMID:Anaphylactoid reaction to imiglucerase, but not to alglucerase, in a type I Gaucher patient. 1038 90

Gaucher's disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multi-system disease which prevalence ranges between 1:30,000 and 1:50,000 in most countries. Thus only a minority of physicians are aware of this diagnosis, of the symptoms that should lead to its consideration, and of the availability of specific tests that confirm it. Because Gaucher's disease often affects the liver, hepatologists may care for Gaucher patients. This review provides the internist and hepatologist with practical information about recent advances in the management of the non-neuronopathic type I of Gaucher's disease. Gaucher's disease, type 1 should be considered when unexplained spleno- and hepatomegaly, anemia, thrombocytopenia, or skeletal disease are present, particularly in combination. The diagnosis is established by an assay for glucocerebrosidase activity in peripheral leukocytes. Lack of awareness and of widespread availability of the enzyme assay has as yet limited its application in clinical practice, and led to many cases of Gaucher's disease being diagnosed by bone marrow and liver biopsy. Alglucerase, placental enzyme preparation of glucocerebrosidase, has proven effective in more than 1,000 patients worldwide. Recently, alglucerase has been exchanged by the recombinant enzyme preparation imiglucerase, which is equally effective and safe. Enzyme replacement improves hematological abnormalities, hepato-splenomegaly, and quality of life in a matter of a few months. Regression of skeletal complications is usually seen only after 3-4 years. Recently gene therapy trials, which center on autotransfusion of retrovirally transduced stem cells, have successfully been started.
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PMID:Gaucher's disease: a review for the internist and hepatologist. 1102 Aug 62

Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous condition affecting multiple organ systems. Patients with nonneuronopathic (type 1) Gaucher disease may suffer from hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Enzyme replacement therapy (ERT) with mannose-terminated glucocerebrosidase (imiglucerase, Cerezyme, Genzyme Corporation, Cambridge, MA) reverses or ameliorates many of the manifestations of type 1 Gaucher disease. However, due to the variable pattern and severity of disease, and the uncertain manner of progression, implementation of treatment, choice of initial and maintenance imiglucerase dose, and evaluation of the therapeutic response must be tailored to the individual patient. For the past 14 years, the US Regional Coordinators of the International Collaborative Gaucher Group have individually and collectively developed extensive clinical experience in managing patients with Gaucher disease. In this review, we present recommendations for initial imiglucerase treatment and subsequent dose adjustments based on a schedule of regular assessment and monitoring, and achievement and maintenance of defined therapeutic goals.
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PMID:Individualization of long-term enzyme replacement therapy for Gaucher disease. 1571 77

The non-random association of Gaucher disease with polyclonal and monoclonal gammopathy has been known since 1950. The effect of treatment on monoclonal gammopathy is not well documented. We report on the long-term evolution of a biclonal gammopathy in a patient with type I Gaucher disease who was treated with splenectomy and enzyme replacement therapy. A 44-year-old man presented with hepatomegaly and massive splenomegaly. Bone marrow aspirate contained typical Gaucher cells and beta-glucosidase was low in peripheral blood leukocytes. Mutations N370S and R120W were detected. Serum protein electrophoresis disclosed two spikes in gammaglobulins. Immunofixation identified two monoclonal components: IgG kappa and IgA kappa. Gammaglobulin concentration was 31.6 g/L. A splenectomy was performed on September 2003 because of massive splenomegaly (9500 g). Two months after the splenectomy, gammaglobulin concentration was 25.2 g/L. Enzyme replacement therapy (Cerezyme 45 UI/kg every two weeks) was prescribed from April 2004 because of significant hepatomegaly and cholestasis. In April 2007 (3 years after the beginning of treatment), serum electrophoresis showed the persistence of two spikes with gammaglobulin concentration at 20.5 g/L. Simultaneously, chitotriosidase activity decreased from 6181 to 2877 nkat/L. Our observation and previous reports suggest that enzyme replacement therapy is more effective in polyclonal hypergammaglobulinaemia than in monoclonal gammopathy.
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PMID:Effect of treatment on biclonal gammopathy associated with Gaucher disease. 1787 46

Gaucher's disease is an inherited lysosomal storage disorder with a deficiency of the enzyme glucocerbrosidase that manifests with clinical features of anemia, hepato-splenomegaly, skeletal destruction and organ dysfunction due to the accumulation of glucocerbrosides. There are several types of Gaucher's disease with varying prognosis and clinical progression of disease. We describe two cases followed at the Aga Khan University, Karachi, Pakistan, with different forms of the disorder. The enzyme Imiglucerase (Cerezyme, Genzyme) has been used to treat Type 1 Gaucher disease while the neuronopathic type has been resistant to therapy. We used Imiglucerase 60 microg/kg every 2 weeks in one patient with Type 1 Gaucher disease and followed hepatic, splenic volumes and blood counts. Treatment with Imiglucerase resulted in a decrease in splenic size, reduced requirements for transfusions and an improvement in cardiopulmonary symptoms.
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PMID:Imiglucerase treatment in Gaucher's disease. 1818 22