Level of residual enzyme activity modulates the phenotype in phosphoglycerate kinase deficiency.

Abstract

OBJECTIVE:

To study the variable clinical picture and exercise tolerance of patients with phosphoglycerate kinase (PGK) 1 deficiency and how it relates to residual PGK enzyme activity.

METHODS:

In this case series study, we evaluated 7 boys and men from 5 families with PGK1 deficiency. Five had pure muscle symptoms, while 2 also had mild intellectual disability with or without anemia. Muscle glycolytic and oxidative capacities were evaluated by an ischemic forearm exercise test and by cycle ergometry.

RESULTS:

Enzyme levels of PGK were 4% to 9% of normal in red cells and 5% to10% in muscle in pure myopathy patients and 2.6% in both muscle and red cells in the 2 patients with multisystem involvement. Patients with pure myopathy had greater increases in lactate with ischemic exercise (2-3 mmol/L) vs the 2 multisystem-affected patients (<1 mmol/L). Myopathy patients had higher oxidative capacity in cycle exercise vs multisystem affected patients (≈30 vs ≈15 mL/kg per minute). One multisystem-affected patient developed frank myoglobinuria after the short exercise test.

CONCLUSIONS:

This case series study of PGK1 deficiency suggests that the level of impaired glycolysis in PGK deficiency is a major determinant of phenotype. Lower glycolytic capacity in PGK1 deficiency seems to result in multisystem involvement and increased susceptibility to exertional rhabdomyolysis.

• Authors: John Vissing, H Orhan Akman, Jan Aasly, Stephen G Kahler, Carlos A Bacino, Salvatore DiMauro, Ronald G Haller
• Journal: Neurology (Neurology) Vol. 91 Issue 11 Pg. e1077-e1082 (09 11 2018) ISSN: 1526-632X [Electronic] United States
• PMID: 30111548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 American Academy of Neurology.

Chemical References

• Lactic Acid
• Phosphoglycerate Kinase

Topics

• Ergometry
• Exercise Test
• Exercise Tolerance (physiology)
• Genetic Diseases, X-Linked (complications, diagnosis, enzymology, physiopathology)
• Humans
• Intellectual Disability (blood, complications, enzymology, physiopathology)
• Lactic Acid (blood)
• Male
• Metabolism, Inborn Errors (complications, diagnosis, enzymology, physiopathology)
• Muscle, Skeletal (metabolism)
• Muscular Diseases (blood, complications, enzymology, physiopathology)
• Phenotype
• Phosphoglycerate Kinase (blood, deficiency, metabolism)