glycogen and Respiratory-Insufficiency

Pompe disease is an autosomal recessive glycogen storage disease caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)-an enzyme responsible for hydrolyzing lysosomal glycogen. GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption. Glycogen accumulation in skeletal muscles, motor neurons, and airway smooth muscle cells is known to contribute to respiratory insufficiency in Pompe disease. However, the impact of GAA deficiency on the distal alveolar type 1 and type 2 cells (AT1 and AT2) has not been evaluated. AT1 cells rely on lysosomes for cellular homeostasis so that they can maintain a thin barrier for gas exchange, whereas AT2 cells depend on lysosome-like structures (lamellar bodies) for surfactant production. Using a mouse model of Pompe disease, the

Topics: alpha-Glucosidases; Glycogen; Glycogen Storage Disease Type II; Humans; Muscle, Skeletal; Pulmonary Surfactant-Associated Protein D; Respiratory Insufficiency

Pompe disease is an extra-rare metabolic storage disease with deficiency of acid-alpha-glucosidase (GAA) enzyme activity, which leads to the pathologic accumulation of glycogen in target tissues (skeletal muscles, heart, brain). Clinical features and severity vary by the age of onset, rate of extent of organ involvement. In the late-onset Pompe disease (LOPD) form, essential cardiomyopathy seems to be uncommon. Muscles weakness and respiratory failure are the main symptoms of adult patient with Pompe disease. In presented case LOPD coupled with patient's regular sporting activity and healthy diet, which may explain the low intensity of the symptoms and the slow progress of the disease, lack of skeletal muscles weakness and lack of brain manifestation. Myocardial storage deposits are the only abnormalities found.

Topics: Glycogen; Glycogen Storage Disease Type II; Humans; Middle Aged; Muscle, Skeletal; Myocardium; Respiratory Insufficiency; Syncope

There is individual variability in the clinical manifestation of McArdle disease, with women generally being more severely affected than men. We compared clinical presentation and exercise capacity between (i) four women with McArdle disease (aged 17, 36, 42 and 70 years) who were also carriers of the K153R variant in the myostatin (GDF-8) gene and in (ii) four women with this disorder matched forage (16, 33, 40 and 69 years), lifestyle, and documented genotype modulators of this disease (ACE, AMPD1 and ACTN3), who did not carry the myostatin variant. Except in the youngest patient, clinical severity was higher in K153R carriers than in their K/K(2) controls (aged 33, 40 and 46 years). Peak cardiorespiratory capacity was very low (< or = 13 mLO(2)/kg/min) in all K153R carriers.

Topics: Actinin; Adolescent; Adult; Aged; AMP Deaminase; DNA Mutational Analysis; Exercise Tolerance; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glycogen; Glycogen Storage Disease Type V; Heterozygote; Humans; Muscle Weakness; Muscle, Skeletal; Mutation; Myostatin; Peptidyl-Dipeptidase A; Phenotype; Respiratory Insufficiency

Topics: Age Factors; Disease Progression; Fatal Outcome; Female; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease Type II; Humans; Infant, Newborn; Lysosomes; Male; Muscle Weakness; Respiration, Artificial; Respiratory Insufficiency; Respiratory Muscles; Treatment Failure; Ventilator Weaning

Topics: Adult; Creatine Kinase; Diagnosis, Differential; Electromyography; Glycogen; Glycogen Storage Disease Type II; Humans; Lysosomes; Male; Muscle Weakness; Muscular Atrophy; Respiratory Insufficiency; Respiratory Muscles; Respiratory Paralysis; Thorax; Tomography, X-Ray Computed

Topics: Glucocorticoids; Glycogen; Glycogen Storage Disease; Humans; Infant, Newborn; Lung; Lung Diseases, Interstitial; Methylprednisolone; Oxygen Inhalation Therapy; Respiratory Insufficiency; Treatment Outcome

Diaphragmatic function and biochemical changes were studied during respiratory failure induced by incremental inspiratory threshold loading in anesthetized rabbits (1) who were unbound and spontaneously breathing, (2) during lower thoracic and abdominal binding, and (3) while bound and undergoing transvenous phrenic nerve pacing of the diaphragm. There was no evidence of contractile fatigue or alterations in glycogen or lactate concentrations in the diaphragm of unbound spontaneously breathing animals. With thoracoabdominal binding, there was a fall in maximal transdiaphragmatic pressure (Pdimax) and the ratio of diaphragmatic force divided by neural input (Pdi/Edi ratio); there was no change in diaphragm glycogen, but there was a significant rise in lactate. In the bound and phrenic-paced animals Pdimax and Pdi/Edi ratio fell, and there was significant glycogen depletion and lactate accumulation. There was a significant correlation between diaphragm function and the levels of diaphragm glycogen and lactate at the point of respiratory failure. We conclude that (1) respiratory failure induced by incremental inspiratory threshold loading was not associated with either contractile fatigue of the diaphragm or diaphragmatic biochemical changes in unbound spontaneously breathing animals, (2) when mechanisms that preserve diaphragmatic function are circumvented by phrenic pacing and/or thoracoabdominal binding, diaphragm fatigue and biochemical changes occur, and (3) there is a significant relationship between in vivo evidence of contractile fatigue of the diaphragm and diaphragmatic glycogen depletion and lactate accumulation.

Topics: Acid-Base Equilibrium; Animals; Carbon Dioxide; Diaphragm; Glycogen; Lactates; Oxygen; Pressure; Rabbits; Random Allocation; Respiratory Function Tests; Respiratory Insufficiency

Eighteen patients with advanced COPD, 8 with chronic respiratory failure (RF) and 10 without (nonRF, NRF) were investigated using spirometry, arterial blood gas analysis and biopsies taken from the quadriceps femorls muscle. The biopsies were analysed for ATP, creatine phosphate (CrP), creatine (Cr), lactate and glycogen content. Muscle fibre composition was also studied. Low concentrations of ATP, glycogen and CrP were found in the RF patients. Significant correlations were found between muscle metabolites and arterial blood gas values with the strongest correlation between muscle glycogen and arterial PO2 (r = 0.70; p less than 0.001). A very low percentage of "oxidative" type I muscle fibres was found in both groups. Possible mechanisms causing depletion of muscle metabolites are discussed.

Topics: Adenosine Triphosphate; Biopsy; Creatine; Female; Glycogen; Humans; Lactates; Lactic Acid; Lung Diseases, Obstructive; Male; Middle Aged; Muscles; Phosphocreatine; Respiratory Insufficiency

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.

Topics: Adult; alpha-Glucosidases; Basilar Artery; Consanguinity; Female; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Intracranial Aneurysm; Muscles; Myocardium; Respiratory Insufficiency; Vacuoles

During the past nine years 10 patients with the adult form of acid maltase deficiency have been observed at the Mayo Clinic. Three of the adults presented with respiratory failure. In all three the respiratory manifestations dominated the clinical picture and the cause of the respiratory failure (muscle weakness) and the underlying myopathy (glycogen storage disease) were initially unsuspected. Careful evaluation of the respiratory function tests, including the maximal static respiratory pressures, electromyographic examination and histochemical and biochemical studies of muscle biopsy specimens eventually led to the correct diagnosis.

Topics: Adult; Electromyography; Female; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Male; Middle Aged; Muscles; Muscular Diseases; Respiratory Function Tests; Respiratory Insufficiency

1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases. 2. On admission, when the patients had marked hypoxaemia, hypercapnia and acidosis, the concentrations of ATP and creatine phosphate were low in both intercostal and quadriceps muscle, particularly the latter. The lactate concentration was increased in relation to control values but glycogen did not differ significantly. 3. In response to therapy, the Pa,CO2 and the patient's acidosis decreased, the vital capacity increased and lung mechanics improved along with the clinical condition. At the same time there were significant increases in the concentrations of ATP, creatine phosphate and glycogen in intercostal and quadriceps muscles, to values similar to, and for glycogen in excess of, those found in control subjects. Lactate concentration fell significantly during treatment. 4. In view of the low initial muscle concentrations of ATP and creatine phosphate in the patients, it is suggested that dysfunction of the respiratory muscles may be an important component of respiratory failure. Moreover, the concentration of energy-rich compounds in muscle rose significantly as the patients responded to treatment, which emphasizes the importance of adequate nutritional therapy in this disorder.

Topics: Acute Disease; Adenosine Triphosphate; Aged; Chronic Disease; Female; Glycogen; Humans; Intercostal Muscles; Lactates; Lung Diseases, Obstructive; Male; Middle Aged; Muscles; Phosphocreatine; Respiratory Function Tests; Respiratory Insufficiency

Topics: Acute Disease; Adenine Nucleotides; Adenosine Triphosphate; Alanine Transaminase; Animals; Aspartate Aminotransferases; Cerebellum; Citrates; Fructosephosphates; Gluconates; Glucose; Glucosephosphates; Glycogen; Hypoxia, Brain; Ischemic Attack, Transient; Ketoglutaric Acids; Lactates; Malates; Male; Medulla Oblongata; Mesencephalon; Mice; Oxygen Consumption; Parietal Lobe; Phosphocreatine; Pons; Pyruvates; Respiratory Insufficiency

Topics: Blepharoptosis; Female; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Infant; Leukocytes; Liver; Muscles; Muscular Diseases; Respiratory Insufficiency

Topics: Carbohydrate Metabolism; Fetal Death; Fetus; Glycogen; Heart; Humans; Infant Mortality; Infant, Newborn; Liver Glycogen; Muscles; Respiratory Insufficiency