Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 22-year-old housewife was referred to us for review of progressive proximal muscle weakness which started at 15 years of age. A biopsy of left rectus femoris muscle showed acid phosphatase positive vacuoles partly filled with PAS-positive material. Acid maltase activity of the cultured fibroblasts was pathologically low at 0.4 nmol/mg protein considering 161.0 +/- 32.4 nmol/mg protein as a normal range. A diagnosis was made of acid maltase deficiency (juvenile type). Western blot using anti-acid maltase polyclonal antibody revealed 115 and 70 kDa bands in control muscles, where as only the 115 kDa band, a presumable precursor of the enzyme, was visualized in the patient. By immunohistochemistry using the same antibody the epitope was localized to the acid phosphatase positive vacuoles and immunoelectron microscopy demonstrated the acid maltase immunoreactivity within lysosomes. We concluded that the protein precursor unable to proceed into mature enzyme can access to lysosomes from endoplasmic reticulum through Golgi complex in the present case.
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PMID:[A case of acid maltase deficiency (juvenile type)--immunohistochemical and biochemical study]. 130 30

Late-onset acid maltase deficiency is a rare disorder. We describe a nineteen year old Chinese girl who presented with diarrhoea, limb-girdle weakness and respiratory failure requiring mechanical ventilation. Electromyography showed polyphasic potentials and myotonic discharges. Muscle biopsy revealed features characteristic of acid maltase deficiency. Assay of acid alpha-glucosidase in cultured skin fibroblasts confirmed the diagnosis. Supportive treatment with nocturnal intermittent positive pressure ventilation via a nasal mask and dietary supplementation with branched-chain aminoacids proved effective in this patient. The cause of diarrhoea remained uncertain. This is the first documented case of acid maltase deficiency in Chinese adult.
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PMID:Late-onset acid maltase deficiency in a Chinese girl. 182 29

Acid maltase deficiency in adults is associated with progressive muscle weakness and may effect respiratory muscles resulting in respiratory failure. The biochemical and clinical manifestations of acid maltase deficiency arise from a marked deficiency of the lysosomal enzyme alpha-glucosidase (acid maltase), which normally degrades glycogen to free glucose. In the past few years, high-protein diets have provided an alternative energy source for these patients and resulted in improved muscle strength. Recently, we treated a ventilator-dependent acid maltase-deficient patient with a general diet supplemented with branched-chain amino acids. Branched-chain amino acids are the principal amino acids involved in muscle protein synthesis and utilization. While on this diet, the patient had improvement of respiratory function and muscle strength and was able to be weaned from the ventilator during the day. In addition to his nutritional status, levels of serum branched-chain amino acids, showed improvement within 2 months after the diet started. This diet shows potential advantages over a high-protein diet without supplemented branched-chain amino acids for the treatment of acid maltase deficiency. These include theoretical sparing of amino acids required for muscle protein synthesis by providing higher concentrations of postprandial branched-chain amino acids in the circulation. Also, the liquid formula would be better tolerated by a ventilator-dependent or debilitated patient rather than a high-protein general diet. Further experience with branched-chain amino acid formulas will be needed to substantiate their efficacy in the treatment of acid maltase deficiency.
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PMID:Treatment of acid maltase deficiency with a diet high in branched-chain amino acids. 211 30

Cardiac failure and skeletal muscle weakness are the main clinical features of glycogenosis type II, a lysosomal storage disorder caused by acid alpha-glucosidase deficiency. In our study, we have investigated in a rat heart perfusion-recirculation system whether acid alpha-glucosidase can be taken up from the vascular system into cardiomyocytes. When rat hearts were perfused with mannose 6-phosphate-containing acid alpha-glucosidase purified from bovine testis, a 3- to 4-fold increase of enzyme activity was obtained. Perfusion with human placental acid alpha-glucosidase not containing the mannose 6-phosphate recognition marker did not have such an effect. The presence of bovine testis acid alpha-glucosidase in heart tissue was demonstrated by immunoblotting. Immunocytochemistry provides evidence for uptake of the exogenous enzyme in lysosomes of the cardiomyocytes. The relevance of these findings for enzyme therapy in glycogenosis type II is discussed.
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PMID:Rat heart perfusion as model system for enzyme replacement therapy in glycogenosis type II. 223 32

We report a 5-year-old boy with lysosomal glycogen storage disease and normal acid maltase activity. This patient, the fourth reported in the literature, was referred to our hospital for evaluation of elevated serum GOT, GPT, and CK activities. He had neither muscle weakness nor atrophy. Echocardiography demonstrated marked thickening of the intraventricular septum and left ventricular wall which indicated hypertrophic cardiomyopathy. Biopsied skeletal muscle disclosed massive accumulation of glycogen and autophagic vacuoles. Electron microscopy of biopsied cardiac muscle revealed severe myofibrillar disruption with marked accumulation of free and intralysosomal glycogen. Activities of all major glycolytic enzymes in skeletal muscle, including acid maltase, were normal. It is unknown why muscle lysosomes appeared to be unable to digest the trapped glycogen despite the presence of acid maltase. Our findings illustrate the importance of performing skeletal muscle investigation during childhood in patients with hypertrophic cardiomyopathy.
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PMID:Glycogen storage disease with normal acid maltase: skeletal and cardiac muscles. 249 94

After the discovery in 1959 of myophosphorylase deficiency, at least 15 myopathies due to deficiency of enzymes involved in energy substrate utilization have been described. In this review two main categories of enzymopathies, glycogenosis and mitochondrial disorders, are discussed. Clinically, the patients with these categories of enzyme defects present two major syndromes: acute recurrent muscle impairment, generally related to exercise, associated with cramps and/or myoglobinuria; progressive muscular weakness and wasting eventually associated with signs of affected organs other than skeletal muscle. Defects of glycogen breakdown and of the first step of glycolysis are more frequently associated with acute exercise intolerance, such as in myophosphorylase and phosphofructokinase deficiencies, but may be associated with progressive muscle weakness and wasting, such as in acid maltase and debrancher enzyme deficiency. Clinical heterogeneity is common in these disorders, but a biochemical explanation for their different clinical expression is still lacking. Defects of the second step of glycolysis, phosphoglycerate kinase, phosphoglycerate mutase and lactate dehydrogenase deficiencies, have been discovered recently and are associated with exercise intolerance. The reason for muscle weakness and atrophy in glycogenosis is still unclear, although it has been suggested that excessive protein catabolism occurs in myophosphorylase, debrancher and acid maltase deficiencies. Myopathies due to deficiencies of mitochondrial enzymes are less well defined, as a group, than the glycogenoses. They are currently considered to fall into three main groups: defects of substrate utilization, such as carnitine palmitoyltransferase deficiency; defects of respiratory chain complexes, such as cytochrome-c-oxidase deficiency and defects of phosphorylation-respiration coupling, such as Luft's disease. Again, severe and benign exercise intolerance or progressive life-threatening myopathic syndromes may be the clinical expression of these disorders. Detailed biochemical and morphological studies of muscle biopsies are needed in these patients to obtain a definite diagnosis and prognosis, and to decide on eventual treatment.
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PMID:Myopathies due to enzyme deficiencies. 293 18

Five adult patients with the myopathic form of acid maltase deficiency are described. In three, the clinical onset dates back from youth with progressive proximal weakness while in the other two, the first symptoms occur after the age of 20 years. Respiratory insufficiency is a direct cause of death in one young adult male and plays an accessory role in the death of an older female patient with an interauricular septal defect. A unilateral diaphragm paralysis is noted in a third patient. A vacuolar myopathy is easily detected in the young adult patients but minimal or moderate lesions are encountered in other muscles or in the older patients. Electron microscopy of muscle and skin biopsies and the assay of acid maltase on muscle completed by the action of antibodies directed against acid maltase represent much more reliable criteria which will confirm the diagnosis. Therefore, when dealing with the heterogeneous group of limb-girdle myopathies, it is necessary to use all adequate diagnostic methods in order to avoid false negative results. The importance of making a correct diagnosis stems from the fact that the respiratory insufficiency should be recognized in order to try to avoid severe complications.
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PMID:Acid maltase deficiency in adults. A study of five cases. 309 Aug 48

An adult patient with lysosomal acid alpha-glucosidase deficiency was fully investigated, and then placed on various forms of therapy with favourable response to a high protein, low carbohydrate diet. The rationale for the employment of this therapy, the problem of acid maltase deficiency and the relationship to weakness and glycogenosome formation with accumulation or otherwise of glycogen within the muscle fibres is discussed.
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PMID:Acid maltase deficiency: a case study and review of the pathophysiological changes and proposed therapeutic measures. 309 39

Two siblings who developed adult form acid maltase deficiency (AMD) are reported. The elder sister, a 30-year-old Japanese woman whose parents are cousins was admitted because of respiratory disturbance which she noticed two years previously. The muscle histology demonstrated numerous acid phosphatase positive vacuoles filled with PAS positive materials, and the muscle enzyme assay demonstrated a reduction of acid maltase activity, thus confirming a diagnosis of acid maltase deficiency of adult form. Her younger sister, a 25-year-old woman who had no obvious history of muscle weakness was admitted because of coma due to subarachnoideal hemorrhage and died two days later. Postmortem examination revealed the rupture of a fusiform aneurysm of the basilar artery whose wall showed vacuolar degeneration, and the histological and biochemical examination revealed that she had also AMD of the adult form. It is considered that the fragility of arterial wall, caused by vacuolar degeneration due to AMD, resulted as the rupture of aneurysm. Immunologically cross reactive material against acid maltase antibody was not detected. To our knowledge, this family is considered to be the third of AMD of the adult form reported in Japan.
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PMID:Adult-onset acid maltase deficiency in siblings. 393 37

The glycogen storage diseases of muscle are the only inherited diseases of muscle in which the biochemical abnormalities are known. Despite impressive advances in knowledge during the past decade there are vital gaps in understanding. In none of these diseases is treatment satisfactory. In none of these disorders can theory relate the symptons of the disease (weakness, cramps, myoglobinuria) to the enzymatic defect. In several there are biochemical abnormalties that do not permit explanation in terms of the enzymatic defect. Individual patients and families do not fit into simple schemes of genetic and biochemical analysis. Different proteins have the same enzymatic activities in different organs, apparently under separate genetic control. One enzyme in particular, acid maltase, plays an uncertain role in the normal metabolism of glycogen; lack of this enzyme in the infantile Pompe's disease and myopathies of later onset are of uncertain significance. For these reasons, and others, there is much to be learned about these diseases wer know best. About more common diseases like the muscular dystrophies, we know even less. It is one thing to deliver medical care and something else to have medical care to deliver.
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PMID:Glycogen storage diseases of muscle problems in biochemical genetics. 428 20


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