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Exercise in muscle glycogen storage diseases

  • Glycogenoses
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Glycogen storage diseases (GSD) are inborn errors of glycogen or glucose metabolism. In the GSDs that affect muscle, the consequence of a block in skeletal muscle glycogen breakdown or glucose use, is an impairment of muscular performance and exercise intolerance, owing to 1) an increase in glycogen storage that disrupts contractile function and/or 2) a reduced substrate turnover below the block, which inhibits skeletal muscle ATP production. Immobility is associated with metabolic alterations in muscle leading to an increased dependence on glycogen use and a reduced capacity for fatty acid oxidation. Such changes may be detrimental for persons with GSD from a metabolic perspective. However, exercise may alter skeletal muscle substrate metabolism in ways that are beneficial for patients with GSD, such as improving exercise tolerance and increasing fatty acid oxidation. In addition, a regular exercise program has the potential to improve general health and fitness and improve quality of life, if executed properly. In this review, we describe skeletal muscle substrate use during exercise in GSDs, and how blocks in metabolic pathways affect exercise tolerance in GSDs. We review the studies that have examined the effect of regular exercise training in different types of GSD. Finally, we consider how oral substrate supplementation can improve exercise tolerance and we discuss the precautions that apply to persons with GSD that engage in exercise.

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Abbreviations

GSD:

Glycogen storage disease

ATP:

Adenosine triphosphate

RPE:

Rate of perceived exertion

PHK:

Phosphorylase kinase

CK:

Creatine kinase

GDE:

Glycogen debranching enzyme

PGM:

Phosphoglucomutase

CDG:

Congenital disorder of glycosylation

PFK:

Phosphofructokinase

NEFA:

Non esterified fatty acid

PGAM:

Phosphoglycerate mutase

GAA:

α-1,4-glucosidase

VO2peak :

Peak oxygen consumption

MET:

Metabolic equivalents

TCA-cycle:

Tricarboxylic acid cycle

ERT:

Enzyme replacement therapy

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Conflict of interest

Dr. Preisler reports having received research support, honoraria, and travel funding from the Genzyme Corporation.

Dr. Haller reports no disclosures.

Dr. Vissing reports having received research support and honoraria from the Genzyme Corporation.

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Authors and Affiliations

  1. Neuromuscular Research Unit, Section 3342, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Nicolai Preisler & John Vissing

  2. Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    Ronald G Haller

  3. Department of Neurology, The Veterans Affairs Medical Center, Dallas, TX, USA

    Ronald G Haller

  4. The Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, TX, USA

    Ronald G Haller

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  1. Nicolai Preisler
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  2. Ronald G Haller
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Correspondence to Nicolai Preisler.

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Communicated by Georg Hoffmann

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Preisler, N., Haller, R.G. & Vissing, J. Exercise in muscle glycogen storage diseases. J Inherit Metab Dis 38, 551–563 (2015). https://doi.org/10.1007/s10545-014-9771-y

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