Document Detail


Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?
MedLine Citation:
PMID:  18401027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M C Ørngreen; H J Schelhaas; T D Jeppesen; H O Akman; R A Wevers; S T Andersen; H J ter Laak; O P van Diggelen; S DiMauro; J Vissing
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Publication Detail:
Type:  Journal Article     Date:  2008-04-09
Journal Detail:
Title:  Neurology     Volume:  70     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-13     Completed Date:  2008-06-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1876-82     Citation Subset:  AIM; IM    
Affiliation:
Neuromuscular Research Unit 7611, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. rh10679@rh.dk
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MeSH Terms
Descriptor/Qualifier:
Chromosomes, Human, X*
Exercise Test
Glycogen / metabolism
Glycogen Storage Disease Type V / genetics,  metabolism
Glycogen Storage Disease Type VIII / genetics*,  metabolism
Glycogenolysis / genetics*
Humans
Lactic Acid / metabolism
Male
Middle Aged
Muscle Weakness / genetics,  metabolism
Muscle, Skeletal / enzymology
Oxidative Stress / genetics
Phosphorylase Kinase / deficiency,  genetics*,  metabolism
Physical Exertion / physiology
Point Mutation*
Protein Subunits / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Protein Subunits; 50-21-5/Lactic Acid; 9005-79-2/Glycogen; EC 2.7.1.19/Phosphorylase Kinase
Comments/Corrections
Comment In:
Neurology. 2008 May 13;70(20):1872-3   [PMID:  18474841 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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