From the Guidelines
The presence of numerous burr cells with low plasma lactate suggests an impairment in pyruvate kinase enzyme activity, which disrupts the final step of glycolysis, preventing the conversion of phosphoenolpyruvate to pyruvate, and subsequently leads to decreased lactate production. This enzyme deficiency is an inherited erythrocyte enzyme disorder that causes hemolytic anemia, as described in the study by Bianchi et al. 1. The metabolic block results in ATP depletion within red blood cells, leading to membrane instability and the characteristic spiculated appearance of burr cells.
Key Points
- Pyruvate kinase deficiency is an inherited erythrocyte enzyme disorder that causes hemolytic anemia, with a worldwide geographical distribution and an estimated prevalence of 5:100 000 in the Caucasian population 1.
- The disease is transmitted as an autosomal recessive trait, with clinical symptoms confined to compound heterozygous and homozygous deficiency patients 1.
- The enzymatic block in pyruvate kinase deficiency occurs before pyruvate formation, resulting in low lactate levels, unlike other glycolytic enzyme defects that typically show elevated lactate levels 1.
- The condition is typically managed with supportive care, including folic acid supplementation, blood transfusions when necessary, and in severe cases, splenectomy may be considered to reduce hemolysis 1.
- Genetic testing can confirm the diagnosis by identifying mutations in the PKLR gene, which is essential for establishing the diagnosis and providing appropriate treatment 1.
Diagnosis and Management
The diagnosis of pyruvate kinase deficiency depends on the demonstration of decreased enzyme activity and/or the identification of causative mutations in the PKLR gene 1. A proposed diagnostic flowchart of hemolytic anemia is shown in Supporting Information Figure S4, which highlights the importance of considering pyruvate kinase deficiency in patients with chronic hemolysis where an immune-mediated hemolytic process, red cell membrane defect, unstable hemoglobin, or paroxysmal nocturnal hemoglobinuria has been excluded.
Conclusion is not allowed, so the answer will be ended here.
From the Research
Enzymatic Conversions Impaired
Based on the findings of numerous burr cells and low plasma lactate, the enzymatic conversions that are likely impaired are:
- Pyruvate kinase activity, as pyruvate kinase deficiency is a common cause of hereditary non-spherocytic hemolytic anemia, which can lead to the formation of burr cells 2, 3
- Other glycolytic enzyme disorders, such as glucose-6-phosphate dehydrogenase deficiency, phosphofructokinase deficiency, and phosphoglycerate kinase deficiency, which can also cause hemolytic anemia and lead to the formation of burr cells 4, 5
Possible Causes of Impaired Enzymatic Conversions
The possible causes of impaired enzymatic conversions in this case are:
- Genetic defects, such as pyruvate kinase deficiency, which can lead to impaired glycolytic enzyme activity 2, 3
- Instability of glycolytic enzymes, such as phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase, which can lead to hemolytic anemia 5
- Oxidative stress, which can lead to the formation of burr cells and impaired glycolytic enzyme activity 2
Relationship between Plasma Lactate and Enzymatic Conversions
The low plasma lactate level in this case suggests that the impaired enzymatic conversions are not related to lactate production, as lactate is an important energy storage molecule that is produced during glycolysis 6. However, the low plasma lactate level may be related to the impaired pyruvate kinase activity, as pyruvate kinase is involved in the conversion of phosphoenolpyruvate to pyruvate, which is then converted to lactate 2, 3.