Phosphofructo-1-Kinase Deficiency Leads to a Severe Cardiac and Hematological Disorder in Addition to Skeletal Muscle Glycogenosis

• DOI: 10.1371/journal.pgen.1000615
• Publication Date: 2009-08-20T21:20:13Z
• Authors: Miguel García; Anna Pujol; Albert Ruzo; Efrén Riu; Jesús Ruberte; Anna Arbós; Anna Serafín; Beatriz Albella; Juan Emilio Felíu; Fátima Bosch
• Keywords: Exercise intolerance; Reticulocytosis

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