glycogen and Hematologic-Diseases

Topics: Acute Disease; Alkaline Phosphatase; Chronic Disease; Glycogen; Hematologic Diseases; Histocytochemistry; Humans; Leukemia; Leukocytes; Lipids; Methods; Peroxidases

Topics: Alkaline Phosphatase; Animals; Brain Edema; Cerebrovascular Disorders; Epilepsy; Glycogen; Guinea Pigs; Hematologic Diseases; Humans; Leukocytes; Neoplasms; Rabbits; Tuberculosis; Wounds and Injuries

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm(-/-)). Here, we show that Pfkm(-/-) mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm(-/-) mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm(-/-) mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm(-/-) mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies.

Topics: Animals; Cardiomegaly; Disease Models, Animal; Erythrocytes; Female; Glycogen; Glycogen Storage Disease Type VII; Hematologic Diseases; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Phosphofructokinase-1

Topics: Anemia, Aplastic; Basophils; Blood Platelet Disorders; Blood Platelets; Bone Marrow; Bone Marrow Cells; Cell Membrane; Cytoplasmic Granules; Endoplasmic Reticulum; Eosinophils; Glycogen; Hematologic Diseases; Humans; Leukemia, Myeloid; Megakaryocytes; Microscopy, Electron; Mitochondria; Neutrophils; Peroxidases; Polyribosomes; Staining and Labeling; Syndrome; Vacuoles

Topics: Anemia; Blood Platelet Disorders; Blood Platelets; Glycogen; Hematologic Diseases; Humans; Myeloproliferative Disorders

Topics: Basophils; Blood Platelet Disorders; Cell Nucleus; Chromatin; Glycogen; Golgi Apparatus; Hematologic Diseases; Humans; Inclusion Bodies; Infections; Leukocytes; Microscopy, Electron; Microtubules; Mitochondria; Neutrophils; Staining and Labeling

Topics: Acyltransferases; Adolescent; Adult; Alkaline Phosphatase; Anemia, Hemolytic; Biliary Tract Diseases; Child; Child, Preschool; Cystic Fibrosis; Erythroblastosis, Fetal; Female; gamma-Glutamyltransferase; Glutamate Dehydrogenase; Glycogen; Hematologic Diseases; Hepatitis A; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Kidney Diseases; Leucyl Aminopeptidase; Neoplasms; Oxidoreductases; Pregnancy

Topics: Blood Cells; Glycogen; Hematologic Diseases; Periodic Acid; Staining and Labeling

Topics: Alkaline Phosphatase; Blood Cells; Child; Child, Preschool; Esterases; Fetal Hemoglobin; Glycogen; Hematologic Diseases; Histocytochemistry; Humans; In Vitro Techniques; Infant; Iron; Leukocytes; Lipids; Peroxidases

Topics: Anemia; Anemia, Hypochromic; Blood Chemical Analysis; Erythrocytes; Glycogen; Hematologic Diseases; Humans; Leukemia, Erythroblastic, Acute; Thalassemia

Topics: Alkaline Phosphatase; Anemia; Anemia, Macrocytic; Anemia, Myelophthisic; Anemia, Pernicious; Clinical Enzyme Tests; Coloring Agents; Glycogen; Hematologic Diseases; Hematology; Histocytochemistry; Leukemia; Periodic Acid; Polycythemia Vera; Staining and Labeling