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.
Neurology. 2018 Sep 11;91(11):e1077-e1082. doi: 10.1212/WNL.0000000000006165. Epub 2018 Aug 15.
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.
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.
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.
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.
研究磷酸甘油酸激酶（PGK）1 缺乏症患者可变的临床症状和运动耐量，以及其与残余 PGK 酶活性的关系。
在这项病例系列研究中，我们评估了 5 个家族的 7 名男孩和成年男性的 PGK1 缺乏症。其中 5 名纯肌肉症状患者，另外 2 名伴有轻度智力障碍，伴或不伴贫血。通过缺血性前臂运动试验和踏车运动试验评估肌肉糖酵解和氧化能力。
纯肌病患者的红细胞 PGK 酶水平为正常的 4%至 9%，肌肉中为 5%至 10%，2 名多系统受累患者的肌肉和红细胞中为 2.6%。纯肌病患者缺血性运动时乳酸升高幅度较大（2-3mmol/L），而 2 名多系统受累患者升高幅度较小（<1mmol/L）。与多系统受累患者相比，肌病患者在踏车运动中具有更高的氧化能力（≈30 比 ≈15mL/kg/min）。1 名多系统受累患者在短运动试验后出现明显的肌红蛋白尿。
本病例系列研究表明，PGK 缺乏症中糖酵解受损的程度是表型的主要决定因素。PGK1 缺乏症中较低的糖酵解能力似乎导致多系统受累，并增加运动性横纹肌溶解症的易感性。
