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Erythrocyte phosphoglycerate kinase deficiency: enzymatic and oxygen binding studies
Insights
X-linked phosphoglycerate kinase (PGK) deficiency causes severe neurological damage in males and hemolytic anemia in both sexes. Compensatory increases in 2,3-diphosphoglycerate improve oxygen delivery, except during crises.
Area of Science:
- Biochemistry
- Genetics
- Hematology
Background:
- Phosphoglycerate kinase (PGK) is an X-linked enzyme crucial for red blood cell energy metabolism.
- Deficiency in red cell PGK can lead to hemolytic anemia and neurological complications.
Purpose of the Study:
- To investigate the clinical manifestations and red blood cell physiology in a kindred with phosphoglycerate kinase deficiency.
- To understand the impact of PGK deficiency on oxygen transport and red cell metabolism.
Main Methods:
- Enzyme activity assays for phosphoglycerate kinase (PGK) in red blood cells.
- Oxygen-hemoglobin equilibrium curve analysis.
- Measurement of red blood cell ATP and 2,3-diphosphoglycerate (2,3-DPG) levels.
Main Results:
- Affected males exhibited severe neurological damage, minimal PGK activity, hemolytic anemia, and decreased red cell ATP.
- Both affected males and older heterozygotes showed elevated red cell 2,3-DPG levels and rightward shifts in oxygen-hemoglobin equilibrium curves.
- Older heterozygotes presented with moderate hemolytic anemia and reduced PGK activity, while a younger heterozygote showed minimal abnormalities.
Conclusions:
- Red cell PGK deficiency is a severe X-linked disorder with variable expressivity in heterozygotes.
- Elevated 2,3-DPG compensates for impaired oxygen delivery in PGK deficiency, mitigating symptoms except during hemolytic crises.
Abstract:
Enzyme and oxygen transport studies have been made on seven members of a kindred with red cell deficiency of phosphoglycerate kinase (PGK), an enzyme known to be linked to the X-chromosome. The two affected males were children, had little detectable PGK activity and had severe neurological damage. Both had moderate haemolytic anaemia complicated by the occurrence of haemolytic crises. Red cell ATP levels were substantially decreased in both subjects. However, they had more than double the normal level of 2,3-diphosphoglycerate (2,3-DPG) in their red cells, associated with a rightward shift in their oxygen-haemoglobin equilibrium curves. This shift in the curve was sufficient to permit oxygen delivery to most body tissues, including the brain, at better tensions than normal, except during a haemolytic crisis. Two of the three known heterozygotes were aged over 70. They had moderate haemolytic anaemia, considerable reduction of red cell PGK activity (19% and 35% of normal, respectively), and considerable increase in red cell 2,3-DPG with rightward shifting of the oxygen-haemoglobin equilibrium curve. The other known heterozygote was aged 22 and showed little abnormality in her blood oxygen transport.