GENETIC DISORDERS OF RED CELL GLYCOLYSIS : A REVIEW FROM THE MOLECULAR TO CLINICAL AND THERAPEUTIC APROACHES

Abstract

The erythrocyte, devoid of nucleus, mitochondria,ribosomes and other organelles, has no capacity for cell replication, protein synthesis, or oxidative phosphorylation. The glycolytic production of ATP,the sole known energy source of erythrocytes is sufficient to meet their limited metabolic requirements. The discovery that hemolytic anemia may result from any of the several glycolytic enzymopathies has underscored the dependence of erythrocytes on glycolysis.(figure 1) Because no specific morphologic abnormality is associated with these disorders they have become known as congenital nonspherocytic hemolytic anemias (CNSHA). Although these anemias are usually transmitted in an autosomal recessive fashion, phosphoglycerate kinase (PGK) is an X-linked abnormality and Adenosine Deaminadase (ADA) excess is an autosomal dominant disorder. Symptoms and signs may be limited to manifestations of hemolysis or of the enzymopathy if it is present in other organ systems. The specific pattern of involvement of nonerythroid tissues may be the real assistance of diagnosis. During the past three decades specific alterations in protein structure have been found to underline many of the enzyme deficiency states and the tools of molecular biology began to identify the genetic basis for these defects. The presence of a glycolytic enzymopathy should be suspected when chronic hemolysis occurs in the absence of identified cause of hemoglobinopathy or spherocytosis.Definitive diagnosis depends on quantitative assay of activity of the suspected enzyme or identification of a specific mutation by DNA analysis. In this review , we discuss the biochemical and genetic basis of the most common erythrocyte enzyme defects.

Keywords

• glycolytic enzymopathies
• chronic hemolysis
• Inherited deficiency
• Hexokinase
• glucose phosphate isomerase
• Phosphofructokinase