期刊
NEUROLOGY
卷 78, 期 4, 页码 265-268出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e31824365f9
关键词
-
资金
- Vanfore Foundation
- A.P. Moller Foundation for the Advancement of Medical Science
- Familien Hede Nielsens Foundation
- Grosserer L.F. Foghts Foundation
- Aase and Ejnar Danielsens Foundation
- Genzyme Corporation
- Hans and Nora Buchards Foundation
- NIH/NICHD
- Marriott Mitochondrial Disorder Clinical Research Fund (MMDCRF)
- Danish Medical Research Council
- Novo Nordisk Foundation
- Ejnar Danielsens Foundation
Objective: To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD). Methods: Patient 1 (39 years old) had mild exercise-induced forearm pain, and EMG showed a myopathic pattern. Patient 2 (69 years old) had raised levels of creatine kinase (CK) for more than 6 months after statin treatment. Both patients had increased glycogen levels in muscle and PHK activity <11% of normal. Two novel pathogenic nonsense mutations were found in the PHKA1 gene. The metabolic response to anaerobic forearm exercise and aerobic cycle exercise was studied in the patients and 5 healthy subjects. Results: Ischemic exercise showed a normal 5-fold increase in plasma lactate (peak 5.7 and 6.9 mmol/L) but an exaggerated 5-fold increase in ammonia (peak 197 and 171 mu mol/L; control peak range 60-113 mu mol/L). An incremental exercise test to exhaustion revealed a blunted lactate response (5.4 and 4.8 mmol/L) vs that for control subjects (9.6 mmol/L; range 7.1-14.3 mmol/L). Fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. None of the patients developed a second wind phenomenon or improved their work capacity with an IV glucose infusion. Conclusion: Our findings demonstrate that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis is probably explained by an alternative activation of myophosphorylase by AMP and P-i at high exercise intensities. Neurology (R) 2012; 78: 265-268
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据