Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous multisystem condition. Patients with non-neuronopathic (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 reverses or ameliorates many of the manifestations of type 1 Gaucher disease. However, the variable disease pattern and severity, and the uncertain manner of progression, render the decision to initiate ERT difficult. Thus, implementation of treatment and evaluation of the therapeutic response must be tailored to the individual patient. To obtain an evidence-based consensus on contemporary therapeutic goals, an international panel of physicians with extensive clinical experience in Gaucher disease met to review the extant literature on its treatment. The panel adopted an integrated system-based approach to arrive at a comprehensive guide to individualized management. Here we establish goals of treatment in Gaucher disease and propose a comprehensive schedule of monitoring of all relevant aspects to confirm the achievement, maintenance, and continuity of the therapeutic response.
 ...
PMID:Therapeutic goals in the treatment of Gaucher disease. 1546 45

Gaucher's disease is the most common lysosomal storage disorder. Gene defect leads to deficiency or decreased activity of glucocerebrosidase followed by the accumulation of glucosylceramide. Most frequently hepatosplenomegaly, anemia, skeletal and hematological abnormalities are present. Different types are known based on the clinical findings. Recently used enzyme replacement therapy seems to eliminate bone marrow transplantation and has favourable effects on symptoms and outcome. Development of gene therapy (reintroduction of missing DNA sequence) hints the possibility of real causal therapy of the disease.
 ...
PMID:[Gaucher's disease: pathogenesis, diagnosis and therapy]. 1549 18

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.
 ...
PMID:Individualization of long-term enzyme replacement therapy for Gaucher disease. 1571 77

Gaucher's disease, rare, hereditary and potentially mortal affection is characterized by the reduced concentration of the glucocerebroside lipid within the macrophage lysosomes. We report the case of a young 2 years old patient treated by transfusion since he was 9 months because of chronic anemia. According the clinical examination, the general state of the patients was bad ith important delayed stanturoponderal growth, a cutaneomucous paller and enormous splenomegaly. The blood count formula showed anemia with major thrombopenia. The myelogram was poor and the osteomedullar biopsy showed the presence of Gaucher's cells. The diagnosis has been confirmed by enzymatic dosage (Leucocytar b-glucosidase). The treatment of the patient has been substitutive enzymatic (inifucerase) with very favorable response. During Gaucher's disease, the enzymatic deficiency results in the pathologic accumulation of the substrate (glucocerebroside) in the lyososomes, this metabolic overloading may cause polyvisceral disease with spontaneous evolution ofter mortal. The recent discovery of a recombining glucocerebrosidase (imiglucerase) transformed the prognosis of this disease.
 ...
PMID:[Gaucher's disease. Substitutive enzymatic treatment in one case and a review of the literature]. 1588 21

Type 1 Gaucher disease (GD) is a progressive lysosomal storage disorder due to an autosomal recessive deficiency of glucocerebrosidase. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone and pulmonary disease. Intravenous enzyme replacement (ERT) with imiglucerase is the accepted standard for treatment of symptomatic patients. More than 3,500 patients worldwide have received ERT with well-documented beneficial effects on the hematological, visceral, skeletal, and pulmonary manifestations, and with resultant improvement in health-related quality of life. Miglustat, an imino sugar that reversibly inhibits glucosylceramide synthase and reduces intracellular substrate burden, is an oral treatment for patients with type 1 GD that was recently approved in the United States for symptomatic patients with mild to moderate clinical manifestations for whom ERT is not an option. Because responses to miglustat are slower and less robust than those observed with ERT, and because miglustat is associated with significant side effects, clinicians who care for patients with GD should become familiar with the limited indications for miglustat use and the circumstances when it may be prescribed appropriately. This review article and position statement represents the current opinion of American physicians with extensive expertise in GD regarding patient management in the context of the availability of standard imiglucerase treatment and the recent introduction of miglustat.
 ...
PMID:Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. 1624 43

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by the deficient activity of glucocerebrosidase. Accumulation of glucosylceramide, primarily in the lysosomes of cells of the reticuloendothelial system, leads to hepatosplenomegaly, anemia and skeletal lesions in type I disease, and neurologic manifestations in types II and III disease. We report herein the identification of hydrophilic active-site-specific chaperones that are capable of increasing glucocerebrosidase activity in the cultured fibroblasts of Gaucher patients. Screening of a variety of natural and synthetic alkaloid compounds showed isofagomine, N-dodecyl deoxynojirimycin, calystegines A3, B1, B2 and C1, and 1,5-dideoxy-1,5-iminoxylitol to be potent inhibitors of glucocerebrosidase. Among them, isofagomine was the most potent inhibitor of glucocerebrosidase in vitro, and the most effective active-site-specific chaperone capable of increasing residual glucocerebrosidase activity in fibroblasts established from Gaucher patients with the most prevalent Gaucher disease-causing mutation (N370S). Intracellular enzyme activity increased approximately two-fold after cells had been incubated with isofagomine, and the increase in glucocerebrosidase activity was both dose-dependent and time-dependent. Western blotting demonstrated that there was a substantial increase in glucocerebrosidase protein in cells after isofagomine treatment. Immunocytochemistry revealed an improvement in the glucocerebrosidase trafficking pattern, which overlaps that of lysosome-associated membrane protein 2 in Gaucher fibroblasts cultivated with isofagomine, suggesting that the transport of mutant glucocerebrosidase is at least partially improved in the presence of isofagomine. The hydrophilic active-site-specific chaperones are less toxic to cultured cells. These results indicate that these hydrophilic small molecules are suitable candidates for further drug development for the treatment of Gaucher disease.
 ...
PMID:Hydrophilic iminosugar active-site-specific chaperones increase residual glucocerebrosidase activity in fibroblasts from Gaucher patients. 1693 36

Type 1 Gaucher disease, the most common lysosomal storage disorder, results from deficiency of glucocerebrosidase causing pathologic accumulation of glucocerebroside. The disease is characterized by marked variation in age of onset and degree of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. Most published data on Gaucher disease come from populations with large proportions of Ashkenazi-Jewish patients, who tend to have less severe disease. We compared selected demographic, clinical, and genetic parameters for Brazilian (N = 221) and rest-of-world (N = 1477) type 1 Gaucher disease patients entered into the ICGG Gaucher Registry since 1991. We also compared Brazilian patients to non-Ashkenazi rest-of-world patients (N = 692) to determine if differences were the result of fewer Brazilian Ashkenazi-Jewish patients (0.5% vs 45.0%). The Brazilian cohort differed significantly (p < 0.05) from the rest-of-world and rest-of-world non-Ashkenazi cohort, respectively, in the following measures: higher proportion of females (59.7% vs 50.4% and 49.7%), lower mean age at diagnosis (17.1 vs 24.1 and 18.8), and higher proportions of patients with anemia (55.5% vs 29.9% and 35.7%), bone pain (57.7% vs 33.7% and 35%), bone crises (16.1% vs 6.5% and 7.4%), and lytic lesions (17.0% vs 7.6% and 7.4%). The most common genotype in Brazil was N370S/L444P (c1448T-->C/c1226A-->C) (46.8% versus 16.3% and 25.7%). These data highlight the genetic and phenotypic heterogeneity among geographic populations of type 1 Gaucher patients and suggest that as a group, Brazilian patients may have a more aggressive form of the disease than rest-of-world patients. The findings also emphasize the need for caution in making generalizations about Gaucher disease across demographic groups.
 ...
PMID:Phenotypic and genotypic heterogeneity in Gaucher disease type 1: a comparison between Brazil and the rest of the world. 1699 65

Gaucher's disease was first described by Philippe Gaucher in 1882, who recognized that this was a systemic disease. The biochemical defect, genetic basis and molecular epidemiology have subsequently been characterized. Gaucher's disease arises as a result of a deficiency of glucocerebrosidase and is the commonest of the lysosomal storage disorders. The overall incidence is approximately 1:40,000 individuals, but it is much commoner amongst individuals of Ashkenazi Jewish origin. A small number of genotypes are characteristically encountered amongst this population and the commonest of these (N370S) encodes an enzyme that has sufficient residual enzyme activity to ensure that significant neurologic disease does not occur. The main clinical features of adult Gaucher's disease are organ enlargement (liver and spleen), bone marrow infiltration leading to anaemia, thrombocytopenia and leucopenia, and skeletal involvement leading to bone pain and pathological fracture. There is also an association with Parkinson's disease, cancer and lymphoproliferative disease, illustrating that Gaucher's disease is a multi-system disorder with manifestations in most organ systems. The underlying pathophysiology is imperfectly understood, but it is increasingly clear that inflammation mediated by cytokines is responsible for a significant part of the pathology.
 ...
PMID:Epidemiology and natural history of Gaucher's disease. 1701 71

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.
 ...
PMID:Imiglucerase treatment in Gaucher's disease. 1818 22

Gaucher disease is a recessively inherited lysosomal storage disorder, caused by deficiency of glucocerebrosidase activity. Affected individuals usually present with hepatosplenomegaly, anaemia, thrombocytopenia, and skeletal diseases. A wide range of neurological manifestations have also been recognized in Gaucher patients including acute neurological deterioration in infancy, mental retardation, ocular motor apraxia, seizure, and parkinsonism. Although muscle weakness is not an uncommon finding in patients with Gaucher disease, the aetiology of weakness is not well understood. We prospectively investigated seven Gaucher patients and found that four of them (patients 1-4) had mild to moderate degree of proximal-predominant symmetrical muscle weakness in four limbs. By history, three patients (patients 1-3) developed insidious onset of nonprogressive muscle weakness in four limbs with easy muscle fatigue from adolescence. A needle electromyographic study detected some small, brief polyphasic waves in these four patients. Muscle biopsy in one patient (patient 1) showed a few atrophic type II muscle fibres without infiltration of Gaucher cells. Three patients (patients 1-3) continuously received enzyme replacement therapy with imiglucerase and their muscle strength seemed improved after two years. We concluded that Gaucher disease may be associated with myopathy.
...
PMID:Myopathy in Gaucher disease. 1819 73


<< Previous 1 2 3 4 5 6 7 8 Next >>