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Published online before print April 9, 2008, doi:10.1212/01.wnl.0000289190.66955.67)
© 2008 American Academy of Neurology Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?From the Neuromuscular Research Unit (M.C.O., T.D.J., S.T.A., J.V.), Department of Neurology, and the Copenhagen Muscle Research Center, Copenhagen, Denmark; Neuromuscular Center (H.J.S., R.A.W., H.J.t.L.), Department of Neurology, University Medical Center Nijmegen, the Netherlands; Department of Neurology (H.O.A., S.D.), Columbia University Medical Center, New York, NY; and Department of Clinical Genetics (O.P.v.D.), Erasmus University Medical Centre, Rotterdam, the Netherlands. Address correspondence and reprint requests to Dr. Mette Cathrine Ørngreen, Neuromuscular Research Unit 7611, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark rh10679{at}rh.dk Objective: It is unclear to what extent muscle phosphorylase b kinase (PHK) deficiency is associated with exercise-related symptoms and impaired muscle metabolism, because 1) only four patients have been characterized at the molecular level, 2) reported symptoms have been nonspecific, and 3) lactate responses to ischemic handgrip exercise have been normal. Methods: We studied a 50-year-old man with X-linked PHK deficiency using ischemic forearm and cycle ergometry exercise tests to define the derangement of muscle metabolism. We compared our findings with those in patients with McArdle disease and in healthy subjects. Results: Sequencing of PHKA1 showed a novel pathogenic mutation (c.831G>A) in exon 7. There was a normal increase of plasma lactate during forearm ischemic exercise, but lactate did not change during dynamic, submaximal exercise in contrast to the fourfold increase in healthy subjects. Constant workload elicited a second wind in all patients with McArdle disease, but not in the patient with PHK deficiency. IV glucose administration appeared to improve exercise tolerance in the patient with PHK deficiency, but not to the same extent as in the patients with McArdle disease. Lipolysis was higher in the patient with PHK deficiency than in controls. Conclusion: These findings demonstrate that X-linked PHK deficiency causes a mild metabolic myopathy with blunted muscle glycogen breakdown and impaired lactate production during dynamic exercise, which impairs oxidative capacity only marginally. The different response of lactate to submaximal and maximal exercise is likely related to differential activation mechanisms for myophosphorylase.
Abbreviations: GSD = glycogen storage disease; PHK = phosphorylase b kinase; RER = respiratory exchange rate.
Supplemental data at www.neurology.org Editorial, page 1872 e-Pub ahead of print on April 9, 2008, at www.neurology.org. Disclosure: The authors report no conflicts of interest. Received May 9, 2007. Accepted in final form August 28, 2007. This article has been cited by other articles:
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