Abstract Details

Title Glycogen Breakdown Is Preserved during Exercise in Severe Muscle Phosphorylase B Kinase Deficiency

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 029

Objective

Background BACKGROUND: Deficiency of muscle phosphorylase b kinase (PhK) has been considered to cause exertional muscle fatigue, cramps, and myogloinuria by impairing the activation of myophosphorylase and limiting glycogenolysis. We evaluated an 18 year-old man with a 3-4 year history of muscle pain, cramps, and fatigue at rest and during exercise and variable mild elevations in serum CK.

Design/Methods DESIGN/METHODS: The patient was evaluated biochemically, genetically and with ischemic forearm and cycle exercise. Results were compared with similar testing in patients with McArdle disease, phosphofructokinase deficiency and distal glycolytic defects.

Results RESULTS: Muscle biopsy revealed a vacuolar myopathy with increased glycogen levels (glycogen = 2.53%, control 1.03±0.13%). Biochemical PhK activity was less than 5% of the control mean attributable to a hemizygous G to A transversion in a highly conserved spice site causing skipping of exon 26 in the PHKA1 gene. With ischemic forearm exercise, the patient developed a normal pattern of fatigue, no muscle contracture and a normal increase in lactate and ammonia. With maximal cycle exercise, lactate and pyruvate increased normally during submaximal and maximal exercise and peak oxygen utilization (VO2) was high normal. During prolonged cycle exercise at 60% of maximal VO2, lactate increased normally, there was no evidence of a 'second wind,' and glucose infused after 30 minutes of exercise elicited no change in perceived exertion or heart rate.

Conclusions CONCLUSIONS: Despite causing increased muscle glycogen levels, PhK deficiency in this patient caused no discernable defect in glycogen breakdown during exercise and none of the characteristic features of exertional fatigue or contractures that are typical of significant defects of muscle glycogenolysis or glycolysis.

Authors/Disclosures
Lydia Sharp, MD PRESENTER	The institution of Dr. Sharp has received research support from McNair Foundation. The institution of Dr. Sharp has received research support from ALS Association.
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Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
Orhan H. Akman, PhD (Columbia University Medical Center)	No disclosure on file
Purificacion Gutierrez Rios, PhD (Columbia University)	No disclosure on file
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Ronald G. Haller, MD	No disclosure on file

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