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)

A biochemical study was performed in a Lapland dog suspected of glycogen storage disease type II (acid alpha-glucosidase deficiency, Pompe's disease). Glycogen content was substantially elevated in heart and skeletal muscle but not in the liver. Severely reduced activities of acid alpha-glucosidase (EC 3.2.1.20) were found in heart, skeletal muscle, liver and cultured tongue fibroblasts. The deficiency was located in the glycoprotein fraction, which supported its lysosomal origin. The electrophorogram showed after acid incubation that the affected dog was missing the activity band, while after neutral incubation the pattern was similar to control. The obtained biochemical data are compared with the known data of the human pathology.
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PMID:Canine glycogen storage disease type II. A biochemical study of an acid alpha-glucosidase-deficient Lapland dog. 704 88

Two mutations in the lysosomal alpha-glucosidase gene, a single base pair deletion (delta T525) and a deletion of exon 18, have recently been identified with a relatively high incidence in Caucasian patients with glycogen storage disease type II (GSD II). Prenatal diagnosis was made in a pregnancy of consanguineous parents of a child with GSD II. The delta T525 deletion was demonstrated in this family but unexpectedly in only one of the parents. The absence of the delta T525 deletion in DNA isolated from the chorionic villi and a normal alpha-glucosidase activity indicated that the fetus was not affected. The possible role of mutation analysis in the prenatal diagnosis of GSD II is discussed in the light of our previous experience from a series of 100 prenatal diagnoses for this disorder by enzyme analysis.
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PMID:Prenatal diagnosis of glycogen storage disease type II: enzyme assay or mutation analysis? 747 85

We performed a clinical, biochemical, and genetic study in 16 patients from 11 families with adult-onset acid maltase deficiency. All patients were compound heterozygotes and carried the IVS1(-13T --> G) transversion on one allele; the second allele harbored either a deletion of a T at position 525 in exon 2 (7 probands, 64%) or a deletion of exon 18 (1 proband, 9%). Deterioration of handicap was related to age, and decrease in vital capacity to duration of the symptomatic stage. Respiratory insufficiency was never the first manifestation. The levels of activity of serum creatine kinase and of alpha-glucosidase in peripheral blood cells or muscle were helpful for the diagnosis, but did not have prognostic value. The adult form of acid maltase deficiency appears to be both clinically and genetically rather homogeneous; decrease of alpha-glucosidase activity is the final common pathway leading to destruction of muscle fibers and progression of muscle weakness over a period of years.
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PMID:Genotype-phenotype correlation in adult-onset acid maltase deficiency. 766 32

We report a 21-year-old man with distal dominant progressive muscle atrophy. The patient was apparently well until 17 years of age when he noted a decrease in exercise tolerance. One year later, he noted difficulty in arising his heels when the walked. He was admitted to our service for the work up in June 10, 1992. On admission, the patient was rather slender in the body build up; otherwise general physical examination was unremarkable. Upon neurologic examination, mental status and higher cerebral functions were normal. In the cranial nerves, the sternocleidomastoid muscles were atrophic bilaterally; other cranial nerves appeared intact. His gait was unstable and he showed steppage gait; walking on toes and heels were impossible. Distal dominant muscle atrophy was noted in both upper and lower extremities. Muscle strength in the deltoid, biceps brachii and triceps brachii was normal. In the lower extremities, both tibialis anterior and triceps surae muscles were weak (3/5). The iliopsoas and quadriceps femoris muscles were normal, however, the adductor muscles of the thigh showed marked weakness (2/5). Myotonia was absent. Deep reflexes were decreased; sensation was intact. Routine blood tests were unremarkable; CK was 96 IU/l, lactate 6.9 mg/dl, and pyruvate 0.61 mg/dl. After an ischemic forearm exercise test, blood lactate level rose to 22.5mg/dl (base line 11.2), and blood ammonia to 88.3 micrograms/dl (base line 71.2). EMG showed myogenic changes and myotonic discharges. A diagnostic biopsy was performed. The patient was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had type III glycogen storage disease. The differential diagnosis included rimmed vacuole type myopathy, Miyoshi type distal muscular dystrophy, Welander type muscular dystrophy, adult type acid-maltase deficiency, and lysosomal glycogen storage disease with normal acid maltase. However, characteristic clinical presentation of initial weakness in the triceps surae muscle associated with atrophy of the sternocleidomastoid muscle confirmed best of the clinical characteristics of type III glycogen storage disease; the only finding which did not fit with its diagnosis was elevation of the blood lactate level after the ischemic exercise test. The muscle biopsy specimen showed marked vacuole formation; approximately 20 to 30% of the vacuoles were rimmed vacuoles, however, the majority was not rimmed. PAS staining on an epon-embedded specimen revealed marked accumulation of PAS-positive materials in those vacuoles as well as in the interfascular space. The non-rimmed vacuoles were not positively stained in the acid-phosphatase staining, which exclude the diagnosis of acid maltase deficiency. No mitochondrial abnormalities were found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A 21-year-old man with distal dominant progressive muscle atrophy]. 778 29

Glycogen storage disease type II (GSDII, Pompe's disease) is caused by an autosomal recessive inheritance of lysosomal alpha-glucosidase deficiency. By sequence analysis we have identified the mutations in the lysosomal alpha-glucosidase gene (GAA) of two unrelated patients, who have one and two copies, respectively, of the same missense mutation. The milder affected adult patient was found to be homozygous for a C1634T transition resulting in the substitution of pro545 by leu. The more severely affected adolescent patient had this same mutant allele combined with a 1 base pair deletion (delta T525) in the second allele causing premature termination at nucleotide positions 658-660. Both these mutations were introduced in wild-type alpha-glucosidase cDNA and expressed in COS-1 cells to analyse their effect. The delta T525 mutation prohibits the formation of lysosomal alpha-glucosidase completely. The pro545-->leu substitution is compatible with normal synthesis but hampers enzyme maturation and results in a 92% net loss of lysosomal alpha-glucosidase activity. The patient with adult GSDII has, in accordance with the allelic constitution, a 2-fold higher residual activity than the patient with juvenile GSDII. The delta T525 deletion was detected in two other unrelated patients, and also the C1634T transition was encountered in two more Caucasian patients with GSDII.
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PMID:The effect of a single base pair deletion (delta T525) and a C1634T missense mutation (pro545leu) on the expression of lysosomal alpha-glucosidase in patients with glycogen storage disease type II. 788 22

Several observations are documented which illustrate that haemopoietic chimaerism is a potential source of error when using assays of cellular components of blood to determine genotype for inherited defects in cattle. Acidic alpha-glucosidase activity in peripheral mononuclear cells of a twin Brahman bull that had sired calves affected with generalized glycogenosis was similar to that in cells from homozygous normal animals. Activity in fibroblasts from this bull was similar to that in heterozygotes. alpha-mannosidase activity in fibroblasts of a twin Murray Grey bull with low activity in peripheral granulocytes but high activity in plasma was similar to that in animals homozygous normal for alpha-mannosidosis. Normal argininosuccinate synthetase nucleotide sequence was detected in leucocytes from two calves affected with citrullinemia and mutant sequence detected in leucocytes from their homozygous normal co-twins.
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PMID:Haemopoietic chimaerism: a complication in heterozygote detection tests for inherited defects in cattle. 816 Oct 14

The lysosomal alpha-glucosidase activity is reduced to 10% to 25% of the average control value in most late-onset cases of glycogen storage disease type II (GSDII). Some adult patients, however, have been identified with an exceptionally low (< 5%) residual enzyme activity. We have investigated one such unusual variant. The rate of alpha-glucosidase synthesis appeared normal but the residual enzyme activity was only approximately 3% in cultured fibroblasts, cultured muscle cells, and muscle tissue of the patient. It appeared that fully matured enzyme molecules were more abundantly present in muscle tissue than in cultured cells. The acid phosphatase activity of affected muscle fibers was enhanced due to an increased number of lysosomes. Lysosomes were particularly abundant in vacuolated areas and they contained, as judged by immunoelectron microscopy, even more alpha-glucosidase molecules than usual. An excessive amount of enzyme molecules were also observed in the endoplasmic reticulum, the site of lysosomal enzyme synthesis, and the cisternae were dilated. These observations suggest that the lysosomal system is stimulated in response to intralysosomal glycogen storage and onset of cellular injury. We hypothesize that the onset of gross pathologic abnormalities is delayed in this particular case of adult GSDII by an increased synthesis of lysosomal alpha-glucosidase, and as a consequence, an increased residual activity in storage-prone muscle fibers.
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PMID:Synthesis and in situ localization of lysosomal alpha-glucosidase in muscle of an unusual variant of glycogen storage disease type II. 825 96

Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. We constructed a plasmid containing a 5'-shortened human acid alpha-glucosidase cDNA driven by the cytomegalovirus promoter, as well as the aminoglycoside phosphotransferase and dihydrofolate reductase genes. Following transfection in dihydrofolate reductase-deficient Chinese hamster ovary cells, selection with Geneticin, and amplification with methotrexate, a cell line producing high levels of the alpha-glucosidase was established. In 48 hr, the cells cultured in Iscove's medium with 5 mM butyrate secreted 110-kDa precursor enzyme that accumulated to 91 micrograms.ml-1 in the medium (activity, > 22.6 mumol.hr-1.ml-1). This enzyme has a pH optimum similar to that of the mature form, but a lower Vmax and Km for 4-methylumbelliferyl-alpha-D-glucoside. It is efficiently taken up by fibroblasts from Pompe patients, restoring normal levels of acid alpha-glucosidase and glycogen. The uptake is blocked by mannose 6-phosphate. Following intravenous injection, high enzyme levels are seen in heart and liver. An efficient production system now exists for recombinant human acid alpha-glucosidase targeted to heart and capable of correcting fibroblasts from patients with Pompe disease.
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PMID:High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease. 855 76

Glycogen storage disease type II (GSD II, Pompe's disease) is an autosomal recessive inherited disease caused by the deficiency of acid alpha-D-glucosidase. In this paper we report two unrelated Chinese patients with infantile form of GSD II who had compound heterozygotes containing a small deletion in one of the acid alpha-D-glucosidase alleles. In both of these compound heterozygotes, one allele contains the C1935A transversion which is the most common mutation in Chinese patients and the other allele contains the newly identified 4 nt deletion of coding sequence (deletion nt 1411-1414). This small deletion causes a reading frameshift and translational premature termination signal in exon 9.
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PMID:Identification of a small deletion in one allele of patients with infantile form of glycogen storage disease type II. 860 85

Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome. Previously we found that acid alpha-D-glucosidase did exist in the skin fibroblasts and there was also no difference of mRNA in quantity and size of Chinese infantile type Pompe disease patients in Taiwan. However, functional assay of the acid alpha-D-glucosidase of these patients showed its enzyme function to be defective. In the present study, first we identified a substitution site in four Chinese infantile patients with Pompe disease which is a cytidine to adenosine (C1935-->A) transversion at 5' end of exon 14 causing substitution of glutamic acid for aspartic acid at position 645 of the acid alpha-D-glucosidase. This substitution was introduced in wild-type cDNA and expressed in COS-1 cells. The Asp-645-->Glu substitution resulted in significant reduction of acid alpha-D-glucosidase activity. Second, according to the screening data in 25 Chinese Pompe disease patients using digestion of RT-PCR amplified specific fragment with Aat II, the restriction fragment length analysis showed that patients presented the 861 bp band and the normal individuals presented the 728 bp and 133 bp polymorphic bands. We found that the frequency of mutant allele is 0.8 in infantile patients with Chinese Pompe disease and 0 in normal individuals. These results therefore indicate that Asp-645-->Glu mutation results in infantile form of Pompe disease as the major cause in Chinese patients in Taiwan.
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PMID:Molecular study on the infantile form of Pompe disease in Chinese in Taiwan. 893 10


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