Pérez M, Foster C, González-Freire M, Arenas J, Lucia A.
One-Year Follow-Up
in a Child With
McArdle Disease:
Exercise is Medicine
Margarita Pérez, MD, PhD*,
Carl Foster, PhD†,
Marta González-Freire, MSc*,
Joaquín Arenas, PhD‡§, and
Alejandro Lucia, MD, PhD*
A 9-year-old boy with McArdle disease, who demon-
strated remarkable recovery of objectively measured
exercise tolerance after 1 year of follow-up, during
which he pursued age-appropriate physical activities.
The patient presented 1 year previously with severe
myalgia, muscle weakness, proteinuria, hematuria, hy-
perthermia, and elevated creatine kinase levels after
noncompetitive swimming. At that time, he reported a
3-year history of general myalgia and poor exercise
tolerance. He was diagnosed with McArdle disease by
both biochemical and genetic methods. Subsequently
he performed a maximal exercise test and was pre-
scribed a return to age-appropriate physical activity
(protected by a pre-exercise dietary consumption of
⬃20 g carbohydrate). At 1-year follow up, he reported
no subsequent acute clinical episodes, no general prob-
lems with exercise either at school or in ordinary
activities, a virtual normalization of serum creatine
kinase levels, and a 14% increase in body mass-
adjusted peak oxygen uptake (from 18.8 to 21.8 mL
O2/kg/min). The results suggest that, with protection
by increasing pre-exercise blood glucose with carbohy-
drate ingestion, a substantially normal lifestyle may be
possible in some children with McArdle disease.
© 2008 by Elsevier Inc. All rights reserved.
From *Department of Exercise Physiology, Universidad Europea de
Madrid, Madrid, Spain; †Department of Exercise and Sport Science,
University of Wisconsin-La Crosse, La Crosse, Wisconsin; ‡Centro de
Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain;
and §Centro de Investigación Biomédica en Red de Enfermedades
Raras, Spain.
© 2008 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2007.10.005 ● 0887-8994/08/$—see front matter
One-year follow-up in a child with McArdle disease:
Exercise is medicine. Pediatr Neurol 2008;38:133-136.
Introduction
McArdle disease (glycogenosis type V) is a relatively
rare disease caused by an inherited deficit of human
muscle glycogen phosphorylase (myophosphorylase)
[1]. This deficit results in blocked muscle glycogenol-
ysis, with subsequent exercise intolerance [2]. An
increased risk of rhabdomyolysis (exacerbated by acute
exertion, e.g., lifting weights), with a subsequent risk of
myoglobinuria, is a common problem in these patients
[3]. Therapeutic options for patients with McArdle
disease have traditionally been limited to recommenda-
tions to adopt a sedentary lifestyle, primarily to prevent
episodes of rhabdomyolysis.
Sedentary behavior may compound the exercise in-
tolerance associated with McArdle disease, and lead to
reduced quality of life. This consideration is especially
important for pediatric patients, given that (1) early
childhood (⬍10 years) is a period of life during which
physical activity habits are established which may
“track” into adulthood, (2) physical and outdoors activ-
ities are an essential part of the daily routine of children
and influence their quality of life, and (3) the plasticity
of body tissues and their adaptability to training are
obviously greater during childhood than at older ages.
Recently, the acute use of pre-exercise carbohydrate
ingestion, designed to increase circulating glucose and
thus allow for blood-derived glycolytic flux, demon-
strated promise [2]. There is also evidence concerning
the mid-term (14 weeks) [4] to long-term (8 months)
benefits of supervised exercise training in adult patients
[5], insofar as this intervention significantly improves
exercise tolerance and overall functional capacity.
The clinical manifestations of McArdle disease were
described in pediatric patients [6-8], but only one recent
report from our laboratory is available on objectively
measured exercise capacity [9]. To our knowledge, there
are no longitudinal or follow-up data available relative to
the value of increased physical activity in pediatric pa-
tients with McArdle disease.
Communications should be addressed to:
Dr. Lucía; Universidad Europea de Madrid (Polideportivo);
28670 Villaviciosa de Odón, Madrid, Spain.
E-mail: alejandro.lucia@uem.es
Received July 19, 2007; accepted October 1, 2007.
Pérez et al: Exercise and McArdle Disease 133
 We report on the 1-year evolution of clinical severity and
exercise capacity of a 9-year-old boy with McArdle disease.
Instead of following a sedentary lifestyle as frequently
recommended, he was able to adopt a normal lifestyle
secondary to using some specific nutritional manipulations,
with only a few specific exercise restrictions.
Case Report
The patient’s parents provided informed consent before testing, and
the study was approved by our institutional ethics committee. From
age 5 years, the patient had complained of marked muscle weakness
and myalgia (predominantly in the legs during uphill walking and
running), easy fatigability, and exercise intolerance, especially during
mandatory physical-education classes. Accordingly, he was generally
less active than most of his peers from a young age. His parents and
relatives had no McArdle-like signs. At age 8 years, he was hospitalized
after an episode of severe myalgia and muscle weakness in both legs,
proteinuria (150 mg/dL), hematuria (250/␮L), hyperthermia, and
elevated serum creatine kinase (4270 U/L) after noncompetitive
swimming [9]. Most signs disappeared after 12 hours. After hospital-
ization, the diagnosis was based on muscle biochemistry (undetect-
able myophosphorylase activity) and molecular genetics (the patient
was homozygous for the common R50X mutation in the PYGM gene).
A histochemical analysis of the muscle biopsy indicated a complete
absence of myophosphorylase staining. The muscle-tissue architec-
ture was preserved, and the majority of muscle fibers were of uniform
size, without structural alterations. Glycogen had accumulated in
small, subsarcolemmal vacuoles and in the intermyofibrillar spaces.
After diagnosis, his parents were initially advised to have the child
refrain from vigorous physical activities (e.g., formal physical edu-
cation or swimming classes) and to follow a sedentary lifestyle.
The child’s energy expenditure during physical activity in the
4-month period between diagnosis and his first visit to our laboratory
was estimated with the metabolic equivalent/minute method, follow-
ing the most recent joint recommendations of the American College of
Sports Medicine and the American Heart Association [10]. Briefly,
one metabolic equivalent/minute represents an individual’s energy
expenditure while sitting quietly for 1 minute, whereas walking at 3
miles per hour (i.e., moderate-intensity activity) and running at 5
miles per hour on a flat, hard surface (i.e., vigorous activity)
represents about 3.3 and 8 metabolic equivalents/minute, respectively.
Most physical activities performed by the child were of light intensity
(⬍3.0 metabolic equivalents/minute, e.g., walking slowly around the
home, and leisure-time occupations). He seldom performed any
moderate-intensity activity (3.0-6.0 metabolic equivalents/minute,
such as walking at a brisk pace or bicycling slowly on a flat surface),
and performed no vigorous activity (⬎6.0 metabolic equivalents/
minute, e.g., basketball or other ball games, or swimming at a
moderate-to-hard pace). Thus, his activity levels were well below the
widely accepted recommendations for health promotion in children,
who should be accumulating ⱖ60 minutes of moderate-to-vigorous
(ⱖ6 metabolic equivalents/minute) physical activity on most or all
days of the week [11].
Four months after diagnosis, the patient and his parents visited our
laboratory (in July 2006) for the patient to perform a graded exercise
treadmill test until volitional exhaustion to determine peak oxygen
uptake, as previously described in detail [9], with pre-exercise (baseline)
and post-exercise blood sampling for lactate, glucose, and serum creatine
kinase activity determination.
After the test, we recommended that he gradually engage in
noncompetitive swimming classes (2-3/week) and join his classmates
in his usual physical-education classes (1-2 per week). Other vigorous
recreational activities (e.g., ball games, or hiking with parents and
friends) were also encouraged. To prevent the occurrence of exercise-
induced rhabdomyolysis, we instructed his physical-education teach-
ers to restrict those specific exercises that involved high local muscle
loads (in particular, lifting weights). His parents, educators, and the
patient himself were instructed regarding oral ingestion of (1) ⬃100
g of complex carbohydrates (pasta, rice, and bread) during breakfast
and lunch to prevent a decrease in blood glucose concentration during
day, and (2) a commercialized sports drink (250-mL solution contain-
ing ⬃20 g of simple carbohydrates, i.e., glucose and fructose) during
the warm-up period before any vigorous exercise (in particular,
physical-education and swimming classes).
We maintained periodic contact with the patient’s parents (once a
month) by telephone. Blood analysis for follow-up of baseline creatine
kinase levels was performed every 4 months until the next visit to our
laboratory, 1 year later (July 2007). During this visit, the patient repeated
the exercise test.
Results and Discussion
The patient did not experience any exercise-related
complications during the 1-year period, during which he
was as physically active as any other child of his age not
competing in sports. Baseline serum creatine kinase
levels decreased and remained well below 1000 U/L
(Fig 1). This is an important finding because, in most
McArdle patients, basal levels of serum creatine kinase
(an indicator of muscle damage) [12] are consistently
elevated even when following a sedentary lifestyle, i.e.,
a mean of ⬃3,000 U/L in male patients [5]. Thus, our
results suggest that reduced chronic muscle damage is
an adaptation to regular physical activity. This is in line
with recent data suggesting that the stimulus of muscle
protein synthesis prompted by exercise training might
counterbalance, at least partly, the muscle-wasting ob-
served in McArdle disease [5]. This is an important
consideration, because evidence continues to accumu-
late that, in most chronic diseases, impaired functional
capacity and exercise intolerance are significantly re-
lated to associated muscle-wasting [13].
Both the patient and his parents reported a significant
improvement in his exercise tolerance, compared with
his exercise tolerance before he visited our laboratory 1
year earlier. He reported an almost total absence of the
Figure 1. Child’s basal levels of serum creatine kinase activity in
different time periods. See text for explanations and examples of “light,”
“moderate,” and “strenuous” physical activities.

134 PEDIATRIC NEUROLOGY Vol. 38 No. 2

“second wind” phenomenon, i.e., unpleasant signs of latter test, it clearly surpassed the mean value of our
early fatigue (e.g., tachycardia or breathlessness) at the laboratory for male patients with McArdle disease (18.7
start of dynamic exercise (such as brisk walking) which mL/kg/min) [5], although it remained below Spanish
disappear after 5-10 minutes of exercise [14]. Basically, norms for age and gender [15]. This result, which reflects
the patient could perform the same types of activities as the beneficial effects of the increase in physical-activity
his classmates, and had adopted a much more positive levels combined with the pre-exercise carbohydrate inges-
attitude (fear-free) toward exercise, which was accom- tion, is clinically relevant, because the peak oxygen uptake
panied by a similar attitude on the part of his parents of McArdle patients is typically very low, and this variable
and teachers. Thus, his physical activity levels had is widely considered the single best indicator of aerobic
increased to ⱖ60 minutes of moderate-to-vigorous ac- physical fitness and is a powerful, independent indicator of
tivities (ⱖ6.0 metabolic equivalents/minute) during 3-4 health status [16].
days per week. He could easily tolerate vigorous activ-
In conclusion, the results of this case study support the
ities that should be part of the daily living of healthy
therapeutic role of routine physical activity and structured
children, such as recreational (noncompetitive) swim-
exercise training, combined with pre-exercise carbohy-
ming (8.0-11.0 metabolic equivalents), ball games com-
drate ingestion, in some children with McArdle disease.
monly included in physical-education classes (e.g.,
recreational soccer, ⬃7.0 metabolic equivalents), and By using simple dietary measures which can partially
tennis (singles, ⬃8.0 metabolic equivalents). Only run- compensate for the underlying metabolic disorder in
ning was less well-tolerated than in his peers, though McArdle disease, and by returning to age-appropriate
this was subjectively attributed to associated breathless- physical activities, our patient was able to recover much of
ness and simple lack of preference (as opposed to his functional ability and quality of life. As such, we
swimming) rather than to any objective muscular prob- believe that this approach deserves a therapeutic trial in
lem. Muscle weakness had disappeared in his upper and children with this disease.
lower limbs (e.g., his arms were strong enough to allow
him to play tennis), and his myalgia was significantly
reduced. He reported no episodes of myoglobinuria, This work was supported by grants PI040487, PI041157, and PI040362
from the Fondo de Investigación Sanitaria. M.G.-F. is also supported by
even during the hours after demanding physical-educa-
the Fondo de Investigación Sanitaria.
tion classes. Finally, he was well-habituated to the
pre-exercise ingestion of the carbohydrate solution on a
daily basis. He did not feel that reliance on this
nutritional intervention (which implied carrying a sports
References
drink with him during most daily hours) affected his
[1] McArdle B. Myophaty due to a defect in muscle glycogen
quality of life or interfered with his normal day-to-day
breakdown. Clin Sci 1951;10:13-33.
living. [2] Vissing J, Haller RG. The effect of oral sucrose on exercise
The patient’s peak oxygen uptake showed ⬃14% im- tolerance in patients with McArdle’s disease. N Engl J Med 2003;349:
provement from the first to second test (Table 1). In the 2503-9.
[3] Martinuzzi A, Sartori E, Fanin M, et al. Phenotype modulators
in myophosphorylase deficiency. Ann Neurol 2003;53:497-502.
[4] Haller RG, Wyrick P, Taivassalo T, Vissing J. Aerobic condi-
Table 1. Comparison of patient’s exercise capacity during 1-year
follow-up tioning: An effective therapy in McArdle’s disease. Ann Neurol 2006;
59:922-8.
[5] Maté-Muñoz JL, Moran M, Pérez M, et al. Favorable responses
8 Years of Age 9 Years of Age
to acute and chronic exercise in McArdle’s patients. Clin J Sports Med
Body mass (kg) 37 38 2007;17:297-303.
Height (cm) 137 143 [6] Colomer Oferil J, Yoldi ME, Vila Torres J. Muscular phosphor-
Baseline (pre-exercise) serum 1570 251 ylase deficiency in two siblings. An Esp Pediatr 1990;32:154-8.
creatine kinase (U/L) [7] Kristjansson K, Tsujino S, DiMauro S. Myophosphorylase
Pre-exercise blood glucose (mg/dL) 93 92 deficiency: An unusually severe form with myoglobinuria. J Pediatr
before sucrose 1994;125:409-10.
Pre-exercise blood glucose (mg/dL) 125 123 [8] Lopez Martin A, Banos Madrid RI, García-Estañ Candela J,
after sucrose
García Pérez B, Pérez Bautista FJ, Salmerón P. McArdle disease: Report
Pre-exercise blood lactate (mmol/L) 0.9 0.8
before sucrose of four brothers with myophosphorylase deficiency. An Med Interna
Results of graded tests 2001;18:136-8.
Test duration 4 min, 20 s 5 min, 50 s [9] Pérez M, Maté-Muñoz JL, Foster C, Rubio JC, Andreu AL,
Peak oxygen uptake (mL O2/kg/ 18.8 21.8 Martín MA, Arenas J, Lucia A. Exercise capacity in a child with
min) McArdle’s disease. J Child Neurol 2007;22:880-2.
Peak blood lactate (mmol/L) 3.0 2.9 [10] Haskell WL, Lee IM, Pate RR, et al. Physical activity and
Peak heart rate (beats/min) 166 190 public health: Updated recommendation for adults from the American
Percent of age-predicted peak 78.3 90.0 College of Sports Medicine and the American Heart Association. Med
heart rate (220 – age)
Sci Sports Exerc 2007;39:1423-34.

Pérez et al: Exercise and McArdle Disease 135

 [11] Cavill NA, Biddle SJ, Sallis JF. Health enhancing physical
activity for young people: Statement of the UK Expert Consensus
Conference. Pediatr Exerc Sci 2001;13:12-25.
[12] Sorichter S, Puschendorf B, Mair J. Skeletal muscle injury
induced by eccentric muscle action: Muscle proteins as markers of
muscle fiber injury. Exerc Immunol Rev 1999;5:5-21.
[13] Stein TP, Wade CE. Protein turnover in atrophying muscle:
From nutritional intervention to microarray expression analysis. Curr
Opin Clin Nutr Metab Care 2003;6:95-102.
136 PEDIATRIC NEUROLOGY Vol. 38 No. 2
[14] Haller RG, Vissing J. Spontaneous “second wind” and glucose-
induced second “second wind” in McArdle disease: Oxidative mecha-
nisms. Arch Neurol 2002;59:1395-402.
[15] San Juan AF, Chamorro-Viña C, Maté-Muñoz JL, et al.
Functional capacity of young children receiving treatment against leu-
kemia. Int J Sports Med [Epub ahead of print] September 18, 2007.
[16] Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood
JE. Exercise capacity and mortality among men referred for exercise
testing. N Engl J Med 2002;4:793-801.