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

Gaucher's disease (GD) is one of the most prevalent lysosomal storage disorders (LSDs) and a rare genetic disease for which specific therapy is now available. GD is an autosomal, recessive, inborn error of glycosphingolipid metabolism, due to a deficiency in the enzyme acid beta-glucosidase. Partial deficiency of acid beta-glucosidase is associated with parenchymal disease of the liver, spleen, and bone marrow with concomitant anemia and thrombocytopenia in non-neuronopathic, type 1 GD. Severe deficiency of glucocerebrosidase caused by severe mutations is additionally associated with neurological manifestations in the less common type 2 and type 3 GD subtypes. Outside of the Ashkenazi Jewish community, a high molecular diversity is observed. Clarification of genotype/phenotype relationship and the identification of modifier loci that impact on GD phenotypes remains a critical area for research. Enzyme replacement therapy (ERT) is proven to be safe and effective in the treatment of type 1 GD, establishing imiglucerase as the current standard of care. Amelioration of hepatosplenomegaly and of hematological manifestations is usually apparent within 6-12 months, whereas the bone disease responds more slowly. ERT cannot reverse the neurological deficits in type 2 or type 3 GD. Small molecule inhibitors of glucosylceramide synthase are being developed for substrate reduction therapy. Other potential therapeutic options such as chaperon-mediated enzyme enhancement therapy and gene therapy are being explored.
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PMID:Gaucher's disease: a paradigm for interventional genetics. 1498 63

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

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.
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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.
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PMID:Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. 1624 43

The treatment of type 1 Gaucher disease has dramatically improved with the development of enzyme replacement therapy (ERT). To date, however, imiglucerase treatment of this disease in Taiwanese pediatric patients has not been reported. A Taiwanese child with type 1 Gaucher disease was regularly treated with imiglucerase beginning October 1998. This 12-year 10-month-old boy had undergone splenectomy when he was 4 years old. He received intravenous imiglucerase 60 U/kg every 2 weeks for 78 months. No signs of pubertal development were documented at the commencement of ERT. There were no serious adverse effects. The patient had significant improvement in skeletal deformity, a dramatic decrease in liver size, markedly increased linear growth, alleviation of bone pain and bone crises, correction of anemia, and improved bone mineral density. ERT with imiglucerase improved the quality of life in this child with type 1 Gaucher disease.
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PMID:Enzyme replacement therapy with imiglucerase in a Taiwanese child with type 1 Gaucher disease. 1683 86

Gaucher disease is an inherited recessive autosomal metabolic defect due to a deficiency of the lysosomal enzyme beta-glucocerebrosidase. The enzyme substrate, glucocerebroside, accumulates in the body, predominantly in the liver, spleen, and bone marrow. Osteoarticular manifestations are often inaugural and contribute much of the morbidity and disability associated with Gaucher disease. There are three types of Gaucher disease. The most common is type 1, which can produce a broad range of presentations characterized by cytopenia and involvement of the spleen, liver, and bone marrow. Types 2 and 3 are rarest variants that manifest in infancy and cause neurologic damages. Patients with type 2 Gaucher disease usually die before 2years of age. beta-glucocerebrosidase assays and examination of bone marrow smears and biopsies ensure the diagnosis. Specific mutations in the beta-glucocerebrosidase gene are associated with specific clinical presentations: thus, the N370S mutation (heterozygous or homozygous) confers type 1 disease and the L444P mutation neurologic involvement and type 3 disease. Bone involvement is a feature in 70%-100% of cases. Abnormal bone remodeling, osteonecrosis and bony infarcts, osteopenia with fractures, and more rarely infections may occur. The other manifestations are dominated by cytopenia (thrombocytopenia, neutropenia, or anemia), hypersplenism, and liver enlargement. The risk of myeloma is increased. Parkinson-like syndromes were recently described in patients with type 1 disease. The enzyme chitotriosidase can be assayed to quantify the degree of macrophage activation. The chemokine CCL18 is another valuable marker but is not readily available in everyday practice. The treatment of Gaucher disease includes symptomatic drugs to relieve pain. Splenectomy is rarely necessary now that specific treatments are available. Enzyme replacement therapy (imiglucerase) has considerably improved the management of the highest risk patients. More recently, an enzyme inhibitor that decreases the production of the substrate (miglustat) was introduced. Chemical chaperone therapy and gene therapy hold promise for the future.
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PMID:Gaucher disease. 1799 73

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.
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PMID:Myopathy in Gaucher disease. 1819 73

Evidence-based therapeutic goals have been developed by European and North American experts in the field of Gaucher disease (GD, lysosomal acid beta glucosidase deficiency, OMIM 230 800) in an attempt to reverse the entire disease phenotype, improve quality of life and prevent life-threatening complications. Patients with GD usually have maximal clinical benefit when enzyme replacement treatment (ERT) efficiency is administered at the optimal time i.e. generally during the asymptomatic phase of the disease. Currently, imiglucerase is the standard of care for type 1 GD due to its high efficiency at improving bleeding tendencies, anemia, reversing heptosplenomegaly and part of skeletal damages and eliminating bone crises. ERT has also demonstrated a remarkable safety profile with tolerability at 3 years greater than 99%. Treatment of GD is a lifelong treatment that patients should not interrupt without a careful monitoring of the disease evolution.
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PMID:[Therapeutic objectives in Gaucher disease]. 1822 83

We present a brief review of Gaucher disease, the most common lysosomal storage disease. Gaucher disease is a rare autosomal recessive disorder characterized by defective function of the catabolic enzyme beta-glucocerebrosidase, leading to an accumulation of its substrate, glucocerebroside, in the mononuclear phagocyte system, especially histiocytes in the spleen, lymph nodes, and bone marrow; Kupffer cells in the liver; osteoclasts in bone; microglia in the central nervous system; alveolar macrophages in the lungs; and histiocytes in the gastrointestinal tracts, genitourinary tracts, and the peritoneum. Clinical signs and symptoms include neurologic dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia, and thrombocytopenia. Enzyme replacement therapy with recombinant glucocerebrosidase is the mainstay of treatment for Gaucher disease, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.
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PMID:Gaucher disease: review of the literature. 1846 35

Gaucher's disease is a rare lipid storage disorder, affecting one in 40,000-200,000 people and results from a genetic deficiency of the enzyme glucocerebrosidase (glucosylceramidase). We report a 10-year old Iranian girl with chief complaint of anemia from 8 years ago, managed for iron deficiency anemia. The patient had hepatomegaly associated with huge splenomegaly which was confirmed by sonography. No skeletal disorder was found. Bone marrow aspiration revealed typical Gaucher cells. Low level of beta-glucocerebrosidase enzyme activity confirmed the Gaucher disease. The patient is now under treatment with CEREZIME, a recombinant DNA modified form of glucocerebrosidase with good condition.
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PMID:Gaucher disease: A 10 year old girl with anemia and huge spelenomegaly (a case report). 1881 Sep 81


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