Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a boy with an early lethal hypertrophic vacuolar cardiomyopathy of neonatal onset. Abnormal intra- and extralysosomal glycogen storage disease was demonstrated in heart and skeletal muscles. Glycogen content was twice the normal in muscles and over 3-fold the normal in the heart. In this organ, over 50% of the intracellular space was occupied by glycogen and possibly oligosaccharides, as demonstrated by the quantitative morphometric analysis of electron micrographs. The activity of acid alpha-glucosidase was increased in the heart, skeletal muscles, and liver, but was normal in leukocytes. A review of the 11 previously published pedigrees of lysosomal glycogen storage disease with normal in vitro alpha-glucosidase activity allows the delineation of three clinical entities: juvenile and neonatal pseudo-Pompe diseases and partial Pompe disease. Partial Pompe disease, due to the tissue-specific absence of acid alpha-glucosidase, was observed in a single patient. The most common form is the late-onset pseudo-Pompe disease, which is characterized by severe cardiomyopathy and mild myopathy appearing in the second or third decade, prominent arrhythmia with Wolf-Parkinson-White syndrome, and sometimes mental retardation. Patients reported as suffering from Antopol disease probably belong to this group. Dominant inheritance (autosomal or X linked) is likely in most families. The present report appears to be the first one to describe a rapidly fatal neonatal form of lysosomal glycogenosis without acid maltase deficiency. The mode of inheritance of this form is not known. Differential diagosis includes Pompe disease (similar histology) and cardiac phosphorylase b kinase deficiency (similar clinical course). The delineation of neonatal pseudo-Pompe disease makes enzymatic confirmation mandatory in each case suspected of Pompe disease.
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PMID:Nosology of lysosomal glycogen storage diseases without in vitro acid maltase deficiency. Delineation of a neonatal form. 938 33

Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists. We investigated the endocytic process in deficient cells of human recombinant GAA produced in Chinese hamster ovary cells, and the potential of GAA-deficient Japanese acid maltase-deficient quail as a model for evaluating the enzyme replacement therapy for Pompe disease. After 24-h incubation with a single dose of recombinant enzyme, intracellular GAA and glycogen levels in deficient human fibroblasts were normalized, and this correction lasted for 7 d. The 110-kD precursor recombinant enzyme was processed to the 76-kD mature form within 24 h after uptake. Intracellular GAA levels in deficient quail fibroblasts and myoblasts were similarly corrected to their average normal levels within 24 h. Differences existed in the efficiency of endocytosis among subfractions of the enzyme, and among different cell types. Fractions with a larger proportion of precursor GAA were endocytosed more efficiently. Quail fibroblasts required a higher dose, 4200 nmol.h-1.mL-1 to normalize intracellular GAA levels than human fibroblasts, 1290 nmol.h-1.mL-1, whereas primary quail myoblasts required 2800 nmol.h-1.mL-1. In all three cell lines, the endocytosed enzyme localized to the lysosomes on immunofluorescence staining, and the endocytosis was inhibited by mannose 6-phosphate (Man-6-P) added to the culture medium. Despite structural differences in Man-6-P receptors between birds and mammals, these studies illustrate that Man-6-P receptor mediated endocytosis is present in quail muscle cells, and demonstrate the potential of acid maltase-deficient quail to test receptor mediated enzyme replacement therapy for Pompe disease.
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PMID:Recombinant human acid alpha-glucosidase corrects acid alpha-glucosidase-deficient human fibroblasts, quail fibroblasts, and quail myoblasts. 950 77

Patients with type Ib glycogen storage disease (GSD Ib) are susceptible to hypoglycaemic episodes. To determine whether an amylase (alpha-glucosidase) inhibitor, voglibose, can be useful in the control of hypoglycaemia, we tried it in a 14-y-old male with GSD Ib. Oral administration of voglibose prolonged the duration of normoglycaemia and reduced the incidence of hypoglycaemia attacks. These findings indicate that voglibose may be useful for preventing hypoglycaemia in GSD Ib patients.
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PMID:Prevention of hypoglycaemia in a patient with type Ib glycogen storage disease by an amylase (alpha-glucosidase) inhibitor. 964 47

Muscle glycogen storage diseases (GSDs) are disorders of inborn error of metabolism, in which gene therapy restoring the deficient enzymes may ultimately cure the diseases. However, considering the pathophysiological basis of GSDs other treatments such as substrate supplementation, activation of the residual enzyme and enzyme replacement, are also important. Therapeutic trials in progress include the combined use of vitamin B6 and cornstarch for GSD type V, enzyme replacement therapy using rh-alpha-glucosidase for GSD type II, and ketogenic diet for GSD type IX.
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PMID:[Therapeutic trials for the patients with muscle glycogen storage diseases]. 1503 88

Glycogen storage disease in the alpha-glucosidase knockout(6neo(-)/6neo(-)) (GAA KO) mouse, a model of Pompe disease, results in the pathologic accumulation of glycogen primarily within skeletal myocytes and cardiomyocytes. Intravenous administration of recombinant human alpha-glucosidase (rhGAA, Myozyme, aglucosidase alfa) can result in significant glycogen clearance from both cardiomyocytes and skeletal myocytes, however, the degree of clearance varies from one skeletal muscle type to another. We sought to determine what role muscle fiber type predominance played in this variability. To examine this question in the GAA KO mouse model we delivered intravenous doses of 100 mg/kg rhGAA on Day 1, and Day 14, and harvested a variety of fast and slow twitch muscles on Day 28. We measured glycogen clearance, muscle fiber type content and capillary density by light microscopy with computer morphometry. Recombinant human-GAA administration resulted in differential clearance of glycogen in the various muscles examined. Slow twitch-predominant muscles cleared glycogen significantly more efficiently than fast twitch-predominant muscles. There was a strong correlation between capillary density and glycogen clearance (r=0.55), suggesting that at the high doses used in this study the differential glycogen clearance observed between muscles is largely due to differential bioavailability of rhGAA regulated by blood flow.
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PMID:Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease. 1757 27

Pompe disease (type 2 glycogenosis, acid maltase deficiency) is a disorder affecting skeletal and cardiac muscle, caused by deficiency of acid alpha-glucosidase. In 2006 enzyme therapy with recombinant human alpha-glucosidase received marketing approval based on studies in infants. Results in older children and adults are awaited. Earlier we reported on the 3-year follow-up data of enzyme therapy in two adolescents and one adult. In the present study these patients were followed for another 5 years. Two severely affected patients, wheelchair and ventilator dependent, who had shown stabilization of pulmonary and muscle function in the first 3 years, maintained this stabilization over the 5-year extension period. In addition patients became more independent in daily life activities and quality of life improved. The third moderately affected patient had shown a remarkable improvement in muscle strength and regained the ability to walk over the first period. He showed further improvement of strength and reached normal values for age during the extension phase. The results indicate that both long-term follow-up and timing of treatment are important topics for future studies.
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PMID:Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease. 1850 67

Pompe's disease is a glycogen storage disease (type II) characterized by inherited autosomal recessive transmission. A 4 month-old girl presented with rapid disease progression, exhibiting severe hypotonia, and hypertrophic cardiomyopathy, progressing to respiratory failure by the age of 9 months. Despite its low incidence, infantile Pompe's disease is lethal. The availability of an effective treatment has created an urgent need to improve knowledge and early diagnosis of this disease. The clinical response is variable from patient to patient with a better effect in patients enrolled earlier. The only clinically available therapy for Pompe's disease is enzyme replacement therapy (ERT). Gene therapy is still not available for Pompe's disease due to lack of suitable vectors for long-term and tissue-specific expression. Recombinant human alpha-glucosidase remains a hope for patients.
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PMID:Enzyme replacement therapy in an infant with Pompe's disease with severe cardiomyopathy. 2033 76

Before 2006, Pompe disease or glycogenosis storage disease type II was an incurable disease whose treatment was merely palliative. The development of a recombinant human alpha-glucosidase enzymatic replacement therapy has become the first specific treatment for this illness. The aim of this guide is to serve as reference for the management of the late-onset Pompe disease, the type of Pompe disease that develops after one year of age. In the guide a group of Spanish experts make specific recommendations about diagnosis, follow-up and treatment of this illness. With regard to diagnosis, the dried blood spots method is essential as the first step for the diagnosis of Pompe disease. The confirmation of the diagnosis of Pompe disease must be made by means of an study of enzymatic activity in isolated lymphocytes or a mutation analysis of the alpha-glucosidase gene. With regard to treatment with enzymatic replacement therapy, the experts say that is effective improving or stabilizating the motor function and the respiratory function and it must be introduced when the first symptoms attributable to Pompe disease appear.
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PMID:Clinical guidelines for late-onset Pompe disease. 2249 3

Glycogen storage disease type II (also called Pompe's disease or acid maltase deficiency) is an autosomal recessive metabolic disorder which causes an accumulation of glycogen in the lysosomes due to deficiency of the lysosomal acid alpha-glucosidase enzyme. It is the only glycogen storage disease with a defect in lysosomal metabolism, and the first glycogen storage disease to be identified in 1932. The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver, and nervous system. We are presenting two cases of infantile form of Pompe's disease with secondary hypertrophic cardiomyopathy (CMP). The first case was a 1-year-old female child who presented with Ross Class III heart failure (HF) of 3 months duration. Echocardiography (ECHO) showed concentric left ventricular (LV) hypertrophy, with the posterobasal segment more hypertrophic than the inter-ventricular septum and moderate pericardial effusion. The second case was a 2-month-old male child who presented with Ross Class II HF. His ECHO showed eccentric hypertrophy of the posterobasal left ventricle, with thickening of the mitral valve leaflets and the chordae with Grade I mitral regurgitation (MR). Both children were diagnosed to have Pompe's disease by blood alpha-glucosidase assay.
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PMID:Two cases of Pompe's disease: case report and review of literature. 2257 6

Glycogen storage disease type 2/Pompe disease is a progressive muscle disorder with a wide range of phenotypic presentations, caused by an inherited deficiency of acid alpha-glucosidase. Since 2004 only a limited number of patients have been treated with recombinant human alpha-glucosidase from rabbit milk whereas since 2006 enzyme replacement therapy (ERT) with alglucosidase alfa has been licensed for the treatment of Pompe disease. This systematic review evaluates the clinical efficacy and safety of alglucosidase alfa treatment of juvenile and adult patients with late-onset Pompe disease (LOPD). Studies of alglucosidase alfa treatment of LOPD patients-published up to January 2012-were identified by electronic searching of the EMBASE and MEDLINE databases, and manual searching of the reference lists. Data on ERT outcomes were extracted from selected papers and analyzed descriptively. No statistical analysis was performed owing to data heterogeneity. Twenty-one studies containing clinical data from 368 LOPD patients were analyzed. Overall, at least two-thirds of patients were stabilized or had improved creatine kinase levels and muscular and/or respiratory function following treatment with alglucosidase alfa. ERT was well tolerated; most adverse events were mild or moderate infusion-related reactions. In conclusion, alglucosidase alfa treatment is effective and well tolerated and attenuates progression of LOPD in most patients. Further research is required to investigate factors such as age at diagnosis, phenotypic presentation, and genotypic characteristics, identification of which may enable better clinical and therapeutic management of LOPD patients.
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PMID:Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review. 2292 64


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