glycogen storage disease type v ( gsd - v ) , also known as mcardle 's disease , is the most common disorder of muscle glycogenosis ( 1 ) .
. therefore , enzyme deficiency results in the defective breakdown of glycogen into glucose and glycogen accumulation in muscle ( 2 ) .
gsd - v is inherited in an autosomal recessive pattern , and the prevalence has been estimated at about 1 in 100,000 - 167,000 ( 3 , 4 ) .
most adult patients present with typical clinical features such as exercise intolerance , episodic myoglobulinuria and the second - wind phenomenon .
in addition , the resting serum creatine kinase ( ck ) level , forearm exercise test , and electrophysiological studies can contribute to diagnosis .
. there has only been one case report of korean patients with gsd - v ( 5 )
. however , the previous report did not feature typical clinical presentations of gsd - v such as myoglobulinuria and the second - wind phenomenon . here , we report a korean case of gsd - v with typical clinical and laboratory findings .
1a , ii-3 ) was referred to our clinic due to easy fatigability , muscle cramps and myoglobulinuria in june 2013 .
she recalled easy fatigability , muscle cramps and contractures after intense exercise during physical education classes since early adolescence .
in addition , she had several episodes of dark urine following intense exercise such as long - distance running
she also reported marked improvement in exercise tolerance after about 20 min , a process termed the ' second - wind phenomenon ' ; specifically , she had seen improvement in excessive fatigue , breathlessness , and tachycardia .
laboratory studies revealed a serum creatine kinase ( ck ) level of 1,161 iu / l ( normal<215
nerve conduction study ( ncs ) and needle electromyography study ( emg ) did not show any abnormalities at rest .
the non - ischemic forearm exercise test showed no increase in venous lactate level with a normal increase in ammonia ( fig .
2 ) . to confirm easy fatigability and weakness after exercise , we performed motor ncs on the ulnar nerve after voluntary maximal contraction for two minutes and 50 hz nerve stimulations for one second .
however , the amplitudes of the compound muscle action potentials did not decrease after maximal contraction and nerve stimulation .
based on the clinical and laboratory features , she was diagnosed with glycogenoses with exercise - induced weakness , especially gsd - v .
a dna sample was extracted from peripheral leukocytes using the quick gene blood kit ( fujifilm , tokyo , japan ) .
the primer set that covers all 20 exons and their flanking intron regions of the pygm was designed with primer 3web v.4.0 ( http://primer3.wi.mit.edu/ ) using sequences from the gen bank accession number nt_167190.1 .
all the exons of the pygm were sequenced using bigdye terminator v.3.1 ( applied biosystems , foster city , ca , usa ) followed by polymerase chain reaction .
electrophoresis and analysis of the reaction mixtures were done with abi3130xl genetic analyzer ( applied biosystems ) .
a compound heterozygous mutation was identified ; one allele had a frameshift mutation of c.1531delg ( p.d510fs ) in exon 13 and the other allele had a deletion mutation of c.2128_2130delttc ( p.f710del ) in exon 17 ( fig .
these mutations have been previously reported to be underlying causes of gsd - v in japanese patients ( 6 ) .
a dna sample was extracted from peripheral leukocytes using the quick gene blood kit ( fujifilm , tokyo , japan ) . the primer set that covers all 20 exons and their flanking intron regions of the pygm
was designed with primer 3web v.4.0 ( http://primer3.wi.mit.edu/ ) using sequences from the gen bank accession number nt_167190.1 .
all the exons of the pygm were sequenced using bigdye terminator v.3.1 ( applied biosystems , foster city , ca , usa ) followed by polymerase chain reaction .
electrophoresis and analysis of the reaction mixtures were done with abi3130xl genetic analyzer ( applied biosystems ) .
a compound heterozygous mutation was identified ; one allele had a frameshift mutation of c.1531delg ( p.d510fs ) in exon 13 and the other allele had a deletion mutation of c.2128_2130delttc ( p.f710del ) in exon 17 ( fig .
these mutations have been previously reported to be underlying causes of gsd - v in japanese patients ( 6 ) .
we described a korean patient with pygm mutations who had typical clinical and laboratory findings for identification of gsd - v . even though gsd - v is the most common disorder of muscle glycogenosis , our patient is only the second case of genetically proven gsd - v in korea .
first , exercise intolerance such as easy fatigability , muscle cramps and contractures is triggered by static contractions and dynamic exercise .
the pathophysiology of exercise intolerance is not fully understood , but may be associated with impaired glycolysis ( 2 ) . a deficient glycogen - dependent adenosine triphosphate
( atp ) supply might result in down - regulation of na / k pumps in myocytes , leading to loss of membrane excitability ( 7 , 8) .
the forearm exercise test showed no increase in lactate level with a normal increase in the ammonia level .
the forearm exercise test was originally carried out under ischemic conditions ; however , we did not conduct the test under ischemic conditions because the diagnostic value is just as good in non - ischemic conditions and muscle injury can be avoided ( 9 ) . in addition , several previous studies demonstrated loss of membrane excitability as the amplitude of cmaps decreased after maximal contracture and high frequency repetitive nerve stimulation , and silent electrical activities during muscle cramping ( 10 , 11 ) .
however , we did not identify these findings in the patient presented in this case study .
second , the serum ck level is elevated in almost all patients with gsd - v even in the absence of exercise .
iu / l ) was present in 99% of patients and the majority ( 79% ) of patients had a level greater than 1,000
the elevation of serum ck level at rest is likely associated with muscle damage due to impaired glycolysis during exercise .
however , the serum ck level at rest did not correlate with clinical severity because exercise - induced muscle damage can stimulate muscle repair and adaptive hypertrophy ( 12 ) .
in addition , one study demonstrated no significant difference in serum ck level at rest between physically active and inactive patients ( 4 ) .
third , about half of all patients with gsd - v have experienced one or more episodes of hyperckemia ( several thousand iu / l ) or myoglobulinuria after intense exercise .
in addition , about 50% of patients with myoglobulinuria develop acute renal failure , which is almost always reversible , but nevertheless requires emergency treatment ( 13 ) .
fourth , the second - wind phenomenon , an especially unique feature of gsd - v , differentiates gsd - v from other muscle glycogenoses such as muscle phosphofructokinase deficiency ( 13 ) .
if it is not found in the medical history , it is easily reproduced by diagnostic cycle test ( 14 ) .
therefore , it is the key finding that leads to initial suspicion of gsd - v .
this phenomenon is caused by an increased supply of glucose and free fatty acids after a long period of exercise .
these changes lead to a switch in metabolic pathways from endogenous glycogenolysis to oxidative phosphorylation of blood - borne fatty acids ( 15 ) .
besides these major clinical features , some patients with gsd - v can also show fixed muscle weakness .
most patients including the patient in this report did not complain of muscle weakness , but approximately one - third of patients develop proximal muscle weakness with aging ( 2 , 16 ) .
mutation analysis and the myophosphorylase activity assay are used to confirm the diagnosis of gsd - v ; however , molecular analysis is more important and more commonly used because muscle biopsy is needed for the enzyme activity assay . at last count in february 2013 , 131 different mutations have been reported in the human gene mutation database ( http://www.hgmd.org ) .
genotype has not been correlated with the severity of clinical phenotype in previous studies ( 17 , 18 ) .
however , there has been a higher incidence of some genotypes in specific ethnic groups ; for example , p.r50x and p.g205s in the white population , p.f710del in the japanese population , and p.w798r in the spanish population ( 13 ) .
likewise , two mutations in our patient have previously been reported in japan , a neighboring country of korea ( 6 ) . in particular , the p.f710del mutation has been identified in 73% of japanese patients ( 19 ) . in conclusion
, we identified a compound heterozygous mutation of the pygm in a korean patient with typical clinical and laboratory findings .
we recognize that detailed clinical and laboratory analysis is only the first step in the diagnosis of disease , especially gsd - v .
 glycogen storage disease type v ( gsd - v ) is the most common disorder of muscle glycogenosis with characteristic clinical and laboratory findings . 
 a 32-yr - old woman complained of exercise intolerance and myoglobulinuria since early adolescence . 
 she reported several episodes of second - wind phenomenon . 
 physical examination did not show any neurological abnormality , including fixed muscle weakness or atrophy . 
 serum creatine kinase level was 1,161 iu / l at rest . 
 the result of the non - ischemic forearm exercise test was compatible with gsd - v . 
 mutation analysis identified the compound heterozygous mutations of the pygm , p.d510fs and p.f710del , which has not yet been reported in korea . 
 the present case recognizes that detail clinical and laboratory analysis is the first step in the diagnosis of gsd-v.graphical abstract 
Graphical Abstract
INTRODUCTION
CASE DESCRIPTION
Mutational analysis
DISCUSSION