Hereditary Red Blood Cell Enzymopathies

Red cell metabolic disturbances result in hemolysis, which leads to a significant shortening of the erythrocyte life span. The most common enzyme deficiencies are glucose 6-phosphate dehydrogenase (G6PD) in the antioxidant pathway, pyruvate kinase in the anaerobic glycolysis pathway, and pyrimidine 5’ nucleotidase (P5’N) in the nucleotide metabolism. While the X chromosome inherits G6PD and phosphoglycerate kinase deficiencies, other enzymopathies show autosomal recessive inheritance. Although the causes of hereditary hemolytic disorders are diverse, clinical, laboratory findings and complications overlap. A history of neonatal jaundice requiring phototherapy and exchange transfusion is quite usual. Mild to severe anemia may be accompanied with episodic or constant hemolysis associated with icterus, hyperbilirubinemia, growth retardation, gallstones, splenomegaly, and a variable degree of iron overload. Erythrocyte enzyme disorders should be suspected in patients with severe hemolytic episodes, or chronic hemolysis, after excluding hemoglobinopathies, membranopathies, and immune-mediated hemolysis.

Effects of methodological variation on assessment of riboflavin status using the erythrocyte glutathione reductase activation coefficient assay

Riboflavin status is usually measured as thein vitrostimulation with flavin adenine dinucleotide of the erythrocyte enzyme glutathione reductase, and expressed as an erythrocyte glutathione reductase activation coefficient (EGRAC). This method is used for the National Diet and Nutrition Surveys (NDNS) of the UK. In the period between the 1990 and 2003 surveys of UK adults, the estimated prevalence of riboflavin deficiency, expressed as an EGRAC value ≥ 1·30, increased from 2 to 46 % in males and from 1 to 34 % in females. We hypothesised that subtle but important differences in the detail of the methodology between the two NDNS accounted for this difference. We carried out an evaluation of the performance of the methods used in the two NDNS and compared against an ‘in-house’ method, using blood samples collected from a riboflavin intervention study. Results indicated that the method used for the 1990 NDNS gave a significantly lower mean EGRAC value than both the 2003 NDNS method and the ‘in-house’ method (P < 0·0001). The key differences between the methods relate to the concentration of FAD used in the assay and the duration of the period of incubation of FAD with enzyme. The details of the EGRAC method should be standardised for use in different laboratories and over time. Additionally, it is proposed that consideration be given to re-evaluating the basis of the EGRAC threshold for riboflavin deficiency.

The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis

The red blood cell depends solely on the anaerobic conversion of glucose by the Embden-Meyerhof pathway for the generation and storage of high-energy phosphates, which is necessary for the maintenance of a number of vital functions. Many red blood cell enzymopathies have been described that disturb the erythrocyte's integrity, shorten its cellular survival, and result in hemolytic anemia. By far the majority of these enzymopathies are hereditary in nature. In this review, we summarize the current knowledge regarding the genetic, biochemical, and structural features of clinically relevant red blood cell enzymopathies involved in the Embden-Meyerhof pathway and the Rapoport-Luebering shunt.