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Muscle phosphorylase kinase deficiency: A neutral metabolic variant or a disease?
MedLine Citation:
PMID:  22238410     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 μmol/L; control peak range 60-113 μmol/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.
Authors:
N Preisler; M C Orngreen; A Echaniz-Laguna; P Laforet; E Lonsdorfer-Wolf; S Doutreleau; B Geny; H O Akman; S Dimauro; J Vissing
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-11
Journal Detail:
Title:  Neurology     Volume:  -     ISSN:  1526-632X     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the Neuromuscular Research Unit (N.P., M.C.Ø., J.V.), Department of Neurology, Rigshospitalet, and the Copenhagen Muscle Research Center, University of Copenhagen, Copenhagen, Denmark; Département de Neurologie (A.E.-L.), Hôpitaux Universitaires, Strasbourg, France; Centre de Référence de pathologie neuromusculaire Paris-Est (P.L.), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Service de Physiologie et d'Explorations Fonctionnelles et EA 3072 (E.L.-W., S.D., B.G.), Hôpital et Université de Strasbourg, Strasbourg, France; and Columbia University Medical Center (H.O.A., S.D.), New York, NY.
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