John Vissing1, H Orhan Akman2, Jan Aasly2, Stephen G Kahler2, Carlos A Bacino2, Salvatore DiMauro2, Ronald G Haller2. 1. From the Department of Neurology (J.V.), University of Copenhagen, Denmark; Department of Neurology (O.A., S.D.), Columbia University, New York, NY; Department of Neurology (J.A.), St. Olavs Hospital; NTNU (J.A.), Trondheim, Norway; Department of Pediatrics (S.G.K.), University of Arkansas School for Medical Sciences, Little Rock; Department of Molecular and Human Genetics (C.A.B.), Baylor College of Medicine, Houston, TX; Neuromuscular Center (R.G.H.), Institute for Exercise and Environmental Medicine of Texas Health Presbyterian Hospital; and Department of Neurology and Neurotherapeutics (R.G.H.), University of Texas Southwestern Medical Center, Dallas. vissing@rh.dk. 2. From the Department of Neurology (J.V.), University of Copenhagen, Denmark; Department of Neurology (O.A., S.D.), Columbia University, New York, NY; Department of Neurology (J.A.), St. Olavs Hospital; NTNU (J.A.), Trondheim, Norway; Department of Pediatrics (S.G.K.), University of Arkansas School for Medical Sciences, Little Rock; Department of Molecular and Human Genetics (C.A.B.), Baylor College of Medicine, Houston, TX; Neuromuscular Center (R.G.H.), Institute for Exercise and Environmental Medicine of Texas Health Presbyterian Hospital; and Department of Neurology and Neurotherapeutics (R.G.H.), University of Texas Southwestern Medical Center, Dallas.
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.
OBJECTIVE: To study the variable clinical picture and exercise tolerance of patients with phosphoglycerate kinase (PGK) 1deficiency 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 myopathypatients 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). Myopathypatients 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: Whitaker Cohn; Chunni Zhu; Jesus Campagna; Tina Bilousova; Patricia Spilman; Bruce Teter; Feng Li; Rong Guo; David Elashoff; Greg M Cole; Alon Avidan; Kym Francis Faull; Julian Whitelegge; David T W Wong; Varghese John Journal: Int J Mol Sci Date: 2022-05-09 Impact factor: 6.208