mcardle's a review report r. salter* · r. h. salter illness: (1) easy fatiguability during...

Postgrad. med. J. (May 1967) 43, 365-371.

McArdle's syndrome:

A review and a preliminary report of four further cases

R. H. SALTER*B.Sc., M.B., B.S., M.R.C.P.

Medical Registrar, Dundee Royal Infirmary

INHERITED enzyme deficiences are increasinglybeing demonstrated as the underlying abnormalityin many hitherto unexplained disease states.Glycogen storage diseases have been shown tobelong to this category, and six types have nowbeen described, each apparently the result of aspecific enzyme defect in the chain of glycogenbreakdown (Mahler, 1966).

In addition to the liver, glycogen is stored involuntary muscle fibres and is the main source ofenergy for anaerobic muscular contraction. Thisis obtained by the generation of adenosine triphos-phate from the breakdown of glycogen to lacticacid via the Embden-Meyerhof pathway, a processinitiated by the enzyme phosphorylase.A defect of muscle glycogen breakdown was first

suggested by McArdle (1951) as the explanation ofa myopathy in a man aged 30 complaining ofmuscular pain, stiffness and weakness on exertion,symptoms which he had noticed all his life.McArdle found that the expected rise in bloodlactate and pyruvate after ischaemic exercise failedto occur. A normal hyperglycaemic response toparenteral adrenaline showed that the breakdownof hepatic glycogen was not impaired and McArdleconcluded that the patient suffered from a disorderof carbohydrate metabolism, affecting chiefly, ifnot entirely, the skeletal muscle.However, the site of the defect in the glyco-

genolytic pathway remained unknown until a pre-liminary communication from Mommaerts et al.(1959) described studies on a muscle biopsy fromthe thigh of a 19-year-old male who had com-plained of muscle cramps and fatiguability onexertion since childhood, and also the passage ofred urine after severe exertion. These workersfound the muscle glycogen content to be greatlyincreased, although the glycogen itself was normalin structure, and there was no detectable myo-phosphorylase activity. It was again shown thatthere was no rise in blood lactate and pyruvate

*Present address: Frenchay Hospital, Bristol.

after ischaemic exercise, a normal hyperglycaemicresponse to parenteral adrenaline, and also animprovement in exercise tolerance after fructoseand glucose infusion (Pearson, Rimer & Mom-maerts, 1961).

In the same year, Schmid & Mahler (1959)investigated a 52-year-old man who had com-plained of easy fatiguability since childhood. Atabout the age of 20 he began to experience cramp-ing pains and weakness in the limb muscles afterexercise, usually followed by the passage of darkurine, the pigment subsequently being identified asmyoglobin. These symptoms were followed overthe next few years by a phase of progressivemuscular weakness, during which time the attacksof cramp and myoglobinuria subsided. Physicalexamination revealed marked muscular wastingand weakness, the proximal muscles of the ex-tremities and the shoulder girdle being particularlyaffected. As in McArdle's patient, there was afailure of the blood lactate to rise after ischaemicexercise, and a normal hyperglycaemic response toparenteral glucagon or adrenaline indicated thathepatic glycogen breakdown was unaffected.Studies of muscle tissue obtained by biopsy showedthe glycogen content to be greatly increased, vary-ing from 2-43 % of the wet weight, and an absenceof any significant activity of phosphorylase.Schmid & Mahler concluded that the disorderwas due to a defect in the phosphorylase systemof skeletal muscle, preventing glycogen breakdownand eliminating anaerobic glycogenolysis as asource of energy for muscular contraction.The family of this patient was investigated

(Schmid & Hammaker, 1961) to try to establishwhether the absence of the enzyme was a here-ditary defect. The parents were first cousins butneither was clinically affected. Of thirteen child-ren, at least three siblings were affected (includingthe propositus) but none of the third generation.Schmid & Hammaker concluded that the defect isdue to a single rare recessive autosomal gene. Bystudying the clinical course of these patients, theyalso suggested that there were three phases of the

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illness: (1) easy fatiguability during childhood andadolescence; (2) the development of crampingpains on exertion followed by transient myo-globinuria during early adult life; and (3) a phaseof weakness and wasting of individual musclegroups from the fourth decade onwards.

Mellick, Mahler & Hughes (1962) reported afurther case of a 17-year-old male, differing onlyfrom the previous patients in that some variationsin the levels of serum aldolase and phosphocreatinekinase were detected, and the muscle glycogencontent was normal and not increased, as hadpreviously been found. They suggested this mightbe due to an additional enzyme deficiency tendingto reduce the rate of glycogen synthesis fromglucose, but not enough material was available toinvestigate this possibility further.A patient described in 1963 (Rowland, Fahn &

Schotland, 1963) showed no new features, but areport in the same year by Engel, Eyerman &Williams (1963) described a late-onset form of thedisease, the symptoms not appearing until thefifth decade. Their first patient was a 52-year-oldwoman who had been free of symptoms until theage of 49, when she, began to complain of pro-gressive generalized muscular weakness and a moreprofound muscular fatigue after exertion. General-ized weakness and muscle wasting were found onphysical examination. The blood lactate failed torise after ischaemic exercise and histologicalexamination of a muscle biopsy revealed a com-plete absence of phosphorylase activity, but theglycogen content appeared normal. A secondpatient aged 60 was the brother of the first, andwas also free of symptoms until the age of 49,when he began to experience cramping muscularpain on exertion relieved by rest. These symptomsdid not progress in severity and were never asso-ciated with pigment in the urine. Muscle bulk andpower were normal on physical examination. Inthis second case there was the usual elevation ofblood lactate to four times the resting level afterischaemic exercise. Muscle biopsy studies againrevealed a normal glycogen content, but somephosphorylase activity was present (about 35% ofthat demonstrated in normal controls). Engel andothers concluded from these studies that partiallyaffected subjects may occur and that the mani-festations may not become apparent until lateadult life.Two further typical cases were described by

Hockaday, Downey & Mottram (1964), and inanother family study, Tobin & Coleman (1965)reported three cases in a family of six siblings.Both groups of workers accepted these findings asfurther evidence for an autosomal recessive in-heritance of the enzyme defect.

Hitherto it was thought that the metabolic defectwas confined to skeletal muscle. However, Ratinov,Baker & Swaiman (1965) described a 19-year-oldmale who had complained of muscular weaknessand cramping on exertion since infancy. He hadnoticed one episode of dark urine after excessivefatigue, but complained of no other symptoms.Examination revealed a healthy looking well-developed young man, and the only features ofnote were a sinus bradycardia (pulse rate 48beats/min) and a grade 1 ejection systolic murmurover the precordium. The diagnosis of McArdle'ssyndrome was confirmed by finding a failure ofthe blood lactate to rise after ischaemic exercise,associated with an increased glycogen content anda virtual absence of phosphorylase activity fromthe skeletal muscle. A chest X-ray showed a nor-mal cardiac shadow, but an ECG revealed sinusbradycardia with marked sinus arrhythmia, a pro-longed P-R interval, intraventricular conductiondelay, increased precordial voltage and T waveinversion in leads V2 and V3. These ECG featureswere similar to those noted by Ehlers & Engle(1963) who analysed the tracings from twenty-oneproven cases of glycogen storage disease involvingthe myocardium. Ratinov et al. (1965) concludedthat the electrocardiographic abnormalities mightbe related to myocardial phosphorylase deficiency,resulting in increased glycogen stores in the myo-cardium, and to a deficiency of the glycolyticsystem upon which the conducting system is be-lieved to be highly dependent. Although this caseis certainly suggestive of heart involvement thereis still no direct evidence of a reduction or absenceof myocardial phosphorylase in McArdle's syn-drome.

Earlier, Rowland et al. (1963) had speculated asto why there was a lack of clinical evidence ofcardiac disorder in this condition. They suggesteda difference between muscle and myocardial phos-phorylase as a possible explanation, or that gly-cogen stores play a small part only in myocardialmetabolism, or that there might be more than oneform of myocardial phosphorylase, so that activityof an alternative enzyme might persist even in theabsence of the form corresponding to that inskeletal muscle.A family study is reported in which four further

cases have been discovered, although one appearsto be only partially affected. The original patientsuffered from attacks of unconsciousness almostcertainly epileptic in origin. Salmon & Turner(1965) also reported a case of a boy aged 16, whowas shown to suffer from McArdle's syndromebut whose presenting feature was a grand malconvulsion, and the relation of the attacks of

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McArdle's syndrome 367

-unconsciousness to the biochemical defect will bediscussed later.These patients will be reported more fully else-

where together with a detailed account of thehistological, histochemical and electron micro-scopic features of the muscle biopsies.

Case reportsCase 1

R.G., age 21, was first seen by a physician at theage of 16 years, when he complained of muscularpain, stiffness and weakness, produced by exertionand relieved by rest. A myopathy was suspected,but physical examination was negative, and amuscle biopsy was reported as normal. No furtherinvestigations were performed at that time, and hewas not seen again until June 1963, when he wasreferred to a surgeon because of episodes ofalleged haematuria, one of which was preceded byan attack of unconsciousness. Thorough investiga-tion of the urinary tract revealed no abnormality.Further attacks followed by the passage of redurine occurred infrequently over the next fewmonths. He was again referred to a physician andadmitted to hospital for further investigation inJanuary 1965.He still complained of muscular weakness, stiff-

ness and pain after exertion, relieved by resting,and also stated that he had had a total of sixattacks, when, after a short bout of severe exertion,he suddenly lost consciousness. Recovery wasassociated with the complaint of generalizedmuscle pains and he also noticed the urine wasred for the next few hours. One of these attacksof unconsciousness was witnessed, and the des-cription was typical of a grand mal convulsion.On examination, he was a healthy looking man,

with no evidence of muscle wasting or weakness.Examination of the chest, cardiovascular system,abdomen and nervous system revealed no abnor-mality.

InvestigationsHaematology, plasma urea and electrolytes,

plasma proteins, urinalysis: no abnormality.ECG: normal tracing.Lumbar puncture: revealed crystal clear fluid

at a pressure of 110 mm CSF. No excess of whitecells.CSF protein, 18 mg/100 ml. CSF sugar, 80 mg/

100 ml. CSF WR negative.EEG: 'Occasional paroxysmal bursts of abnor-

mality consisting of sharp waves or spikes andslow waves suggesting the possibility of epilepsy'(Dr R. S. Bluglass).EMG: 'Within normal limits both at rest and

after pain had been produced in the quadriceps

femoris muscle by severe exertion' (Dr J. A. R.Lenman).

Glucose tolerance test, glucagon stimulation test,intravenous tolbutamide test: no abnormality.Blood lactate before and after ischaemic exercise

(McArdle, 1951)Before exercise After exercise

Patient 14-5 mg/100 ml 17 mg/100 mlControl 9 5 mg/100 ml 37 5 mg/100 ml

Muscle biopsy: Histology showed vacuolationof the muscle fibres, many vacuoles containingmaterial giving a positive reaction with stainsspecific for glycogen (Dr A. Todd).These features are recognized to be charac-

teristic of McArdle's syndrome (Pearce, 1965).In view of this finding, the histology of the pre-

vious muscle biopsy taken in 1961 was reviewed.Several vacuoles were seen which at that time werethought to be due to fixation artefacts, but in thelight of the more recent findings, are now con-sidered to be characteristic of McArdle's syndrome(Dr A. Todd).

TABLE 1

Summary of results of affected siblings

Blood lactate(mg/100 ml) Muscle biopsy

Age Before After Glycogen Phosphorylase(years) ischaemic ischaemic content activity

exercise exerciseR.G.

(original 21 14-5 17-0 3-92 None detectedpatient)H.U.

(sister) 39 6 5 6 5 4-05 None detectedE.G.

(brother) 27 7-0 8 5 1*16 DiminishedC.G.

(brother) 38 7-5 8-0 -

Glycogen content expressed as mg/100 mg muscle (wetweight). Normal value approximately 1-0 mg.

Histochemical studies (Table 1) revealed anexcess of glycogen and no significant phosphory-lase activity was detected (Dr G. W. Pearce).

ProgressWhen the diagnosis was established, the patient

was treated with fructose 40 g to be taken thrice-daily or before any severe exertion as suggestedby Mellick et al. (1961).However, as this produced no significant im-

provement and caused considerable weight gain, itwas discontinued after a few months.

Since his discharge from hospital, he has hadtwo further attacks of unconsciousness followedon recovery by generalized muscle pain and thepassage of red urine. Spectroscopy of the urine onthese occasions has confirmed the presence of



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myoglobin. One attack was precipitated by exer-tion, but the other occurred while at rest. When hewas examined after the latter, some small tonguelacerations were noted. Otherwise, his generalhealth has been maintained, and the only difficultyencountered has been finding some suitable lightemployment.

Case 2C.G., age 38 years, had complained of muscular

pain and stiffness on exertion, relieved by rest,since childhood. These symptoms were particularlytroublesome during his period of National Service,and as repeated medical examinations were alwaysnegative, he was frequently accused of being amalingerer. His symptoms seem to trouble himlittle at present, and he works as a charge handin a Midlands steelworks. He has never had attacksof unconsciousness or passed red urine, and he hadno other complaints.

Physical examination revealed no abnormality,in particular there was no muscle weakness orwasting.


blood sugar, plasma proteins, chest film, ECG andurinalysis: no abnormality.Blood lactate before and after ischaemic exercise

(McArdle, 1951)Before exercise After exercise

Patient 7-5 mg/100 ml 8 mg/100 mlControl 9 0 mg/100 ml 15 mg/100 ml

As this patient lives in the Midlands, musclebiopsy was not possible but the clinical featuresand blood lactate results are typical of McArdle'ssyndrome.

Case 3E.G., age 27 years, also complained of muscular

pain and stiffness after exertion and relieved byrest, since childhood, but his symptoms were notparticularly severe, and while doing his NationalService with the Royal Artillery, he had no realdifficulty with route marching and was a keenboxer.At present he still experiences cramps in the

calves while walking up hills although this symp-tom is rarely severe enough to make him stopwalking. He has noticed no pain after use of othermuscle groups. Also, he has never had attacks ofloss of consciousness or passed dark urine.

Physical examination revealed no abnormality,again there being no evidence of muscular weak-ness or wasting.


blood sugar, plasma proteins, chest film, ECGand urinalysis: no abnormality.

Blood lactate before and after ischaemic exercise(McArdle, 1951)

Before exercisePatient 7 mg/1100 mlControl 7 mg/100 ml

After exercise8-5 mg/100 ml15 5 mg/100 ml

Muscle biopsy: the routine histological prepara-tion suggested a slight myopathy (Dr G. W.Pearce).

Histochemical studies (Table 1) revealed a slightexcess of glycogen and diminished phosphorylaseactivity.

Case 4H.U., age 39 years, was well during her early

childhood and while at school, but from the age of13 years began to complain of shortness of breathand tiredness on exertion. A diagnosis of mitralstenosis was made at this time. The complaint ofbreathlessness on exertion became steadily moremarked, and at the age of 30 she was admitted toDundee Royal Infirmary, and a mitral valvotomywas performed (Professor D. Douglas). The opera-tion was technically very successful, a good valvesplit being obtained, but she herself felt no realbenefit. She was subsequently admitted to hospitalfor investigation of this failure to improve, but nodefinite conclusions were reached. When admittedto hospital in February 1966 for further investiga-tion, she complained of still feeling generally un-well with tiredness and shortness of breath pre-cipitated by exertion. She admitted to no attacksof unconsciousness or episodes of passing darkurine. She noticed that the left forearm musclesbecame painful and hard after exertion, but similarsymptoms were not produced after use of othermuscle groups.On examination there was a malar flush but she

was not cyanosed or breathless at rest. Examina-tion of the cardiovascular system revealed signsof mitral stenosis. No significant abnormality wasfound on examination of the chest, abdomen andnervous system, and there was again no evidenceof muscular weakness or wasting.

InvestigationsHaemoglobin 12-1 g/100 ml. White cell count,

11,300/mm3 (neutrophils at the upper limit ofnormal). ESR (Wintrobe), 28 mm/hr. Randomblood sugar, 90 mg/100 ml. Plasma urea andelectrolytes: normal figures. Serum albumin,3 5 g/100 ml. Serum globulin, 4*3 g/100 ml.ECG: Normal tracing.Chest X-ray: showed the transverse diameter of

the heart and the vascular pattern of the lung fieldsto be within normal limits. Oblique and lateral

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views with barium showed slight enlargement ofthe left atrium but no other specific chamber en-largement was shown, and no definite valvularcalcification was seen.

Blood lactate before and after ischaemic exercise(McArdle, 1951)

Before exercise After exercisePatient 6-5 mg/100 ml 6 5 mg/100 mlControl 6 5 mg/100 ml 17-5 mg/100 ml

Muscle biopsy: Histology showed the charac-teristic features of McArdle's syndrome and histo-chemical studies (Table 1) revealed a considerableexcess of glycogen and an absence of phosphory-lase (Dr G. W. Pearce).

Parents and remaining siblingsThe parents and remaining two siblings of the

original patient (R.G.) were also investigated.None had any muscle symptoms, physical exam-ination was negative, and all had a normal eleva-tion of blood lactate after ischaemic exercise. Theblood lactate results are summarized in Table 2.

TABLE 2

Summary of results of parents and unaffected siblings

Blood lactate (mg/100 ml)

Age(years) Before ischaemic After ischaemic

exercise exercise

Joseph G. 61 5-3 20 3(Father)Janet G. 59 5 0 13-5(mother)Mary S. 40 5-0 12-0(sister)Joseph G. 30 8-5 17-5(brother)

DiscussionFour siblings suffering from McArdle's syn-

drome are described, although Case 3 (E.G.)appears to be only partially affected. His symptomsare certainly less severe than Cases 1 and 2, andthis minor clinical involvement is reminiscent ofthe second case described by Engel et al. (1963),in which muscle biopsy studies also showeddiminished rather than absent phosphorylaseactivity, and a glycogen content of 1-1% (wetweight). The two cases differ, however, in that thesymptoms of the latter did not commence until theage of 49, and there was a normal elevation ofblood lactate after exercise to four times the rest-ing level.

That the clinical condition is not always a re-liable guide in assessing whether there is a partialor total deficiency of phosphorylase is demonstratedby Case 4. Although it might be imagined that

because of the rheumatic heart disease she couldnot exert herself sufficiently to develop muscularsymptoms, the cardiac lesion is not severe, and sheworks full-time in an electrical appliance factoryin addition to performing the usual householdduties. As already stated, muscle biopsy studiesrevealed no phosphorylase activity, and a grosslyelevated glycogen content. Despite this she admit-ted to virtually no specific muscular symptoms, hercomplaints being rather of tiredness and generalmalaise.

Evidence that the site of glycogen depositionrather than the total amount present in the muscleis more important in the production of symptoms,has been obtained by Schotland et al. (1966). Theirelectron microscopic studies on muscle from apatient with McArdle's syndrome showed thatglycogen was deposited primarily in the intermyo-fibrillar space of the I band, under the sarcolemma,between the thin filaments within the I band, andoccasionally between the filaments in the A band.Similar studies on the cases forming the basis ofthis report will be published later.The suggestion from previous family investiga-

tions that the biochemical defect is inherited by asingle recessive autosomal gene has been confirmedby this study. Parental consanguinity is often acontributing factor, but the parents in this studystated that, to the best of their knowledge, theirfamilies were unrelated.One of the main features of Case 1 was the

attacks of loss of consciousness resembling grandmal convulsions, usually precipitated by severeexertion and followed both by generalized musclepains and transient myoglobinuria. There was nofamily history of epileptic disorders, but, as alreadystated, the EEG showed features suggesting thispossibility. A similar association of an attack withMcArdle's syndrome was reported by Salmon &Turner (1965). They described a boy aged 16 whohad a grand mal convulsion 15 min after startinga game of basket-ball, and shortly afterwardspassed dark urine, the pigment being identified asmyoglobin. He admitted to easy fatiguability inthe past, but complained of no other symptoms. Asister had had convulsions associated with febrileillnesses during infancy, otherwise there was nofamily history of seizures. Physical examinationrevealed no abnormality except for minimal weak-ness of the shoulder and pelvic girdle muscles, andalso of the extensors of the toes and wrists. Theblood lactate failed to rise after ischaemic exercise,and histochemical studies of a muscle biopsy re-vealed no phosphorylase activity, and a normalglycogen content. An EEG on the day of admis-sion showed a paroxysmal slowing of activity,particularly after hyperventilation, and a repeat



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examination 7 weeks later showed the abnormalitywas persistent.Salmon & Turner considered the following three

possible explanations of the association of theseizure with McArdle's syndrome and their re-marks apply equally to Case 1 of the presentreport:

(1) It is conceivable that the association is merelycoincidental as idiopathic epilepsy is such a com-mon condition. The seizure might thus have beenprecipitated by fatigue and the succeeding musclesymptoms and myoglobinuria, the result of theconvulsive movements.

(2) The convulsive threshold might be loweredby the effects of circulating muscle breakdownproducts.

(3) As a result of the enzyme deficiency,glycogen cannot be broken down. Energy for mus-cular contraction during severe exertion mighttherefore be obtained by the excessive utilizationof glucose which can enter the glycogenolyticpathway beyond the stage where phosphorylase isrequired. Although hepatic glycogenolysis is un-affected, this might result in hypoglycaemia whichcould precipitate a convulsion.The second explanation would seem unlikely as

there are no reports of seizures occurring in asso-ciation with episodic muscle breakdown from othercauses similarly resulting in the liberation ofmyoglobin and other substances. Coincidentalidiopathic epilepsy is impossible to exclude, andthe recorded EEG abnormalities might be due toan underlying convulsive disorder. However, thethird explanation, suggesting an hypoglycaemicbasis for the convulsions, is attractive, and theEEG abnormalities could equally well be a reflec-tion of brain damage as a result.The observation that only some, rather than all,

patients with myophosphorylase deficiency experi-ence attacks of myoglobinuria, remains to beexplained. Rowland et al. (1963) presumed it mightbe related to an inability to maintain adequatelevels of adenosine triphosphate (ATP) to pre-serve the integrity of the sarcolemmal membrane.However, biochemical studies on muscle biopsiesfrom two patients known to suffer from McArdle'ssyndrome, both while resting and after the induc-tion of a contracture, showed no significant changein ATP concentration (Rowland, Araki & Carmel,1965).As previously mentioned, Schmid & Hammaker

(1961) divided the clinical course of patients suffer-ing from myophosphorylase deficiency into threephases-easy fatiguability during childhood fol-lowed by cramping muscular pains after exertion(with or without myoglobinuria) during early adultlife and a final myopathic phase from the fourth

decade onwards. Many of the patients reportedwith this syndrome have not been observed longenough to confirm this description of the naturalhistory. However, the siblings forming the basisof the present study do not support these con-clusions. As Case 3 is only partially affected it canhardly be expected that the typical course wouldbe followed, but Cases 2 and 4, aged 38 and 39respectively, have shown no variation in theirsymptoms over the years, and there has certainlybeen no deterioration in their condition. They mayyet progress to a myopathic phase, but this doesnot seem likely. Case 1, however, is the mostseverely affected, and the only member of thefamily to experience attacks of myoglobinuria.This may well represent Schmid & Hammaker'ssecond phase, and the possibility of permanentmuscle wasting and weakness in later years seemsmore probable.

It can be seen from this brief review that sinceMcArdle's original description of the condition(McArdle, 1951), patients have been reported pre-senting in ways other than with muscular pain andstiffness on exertion. Also partially affected formsmay occur, there being a reduction rather than acomplete absence of myophosphorylase activity.Even when the presentation is typical, diagnosisis often delayed as physical signs are lacking, andthe patients are frequently dismissed as neuroticor hysterical. The possibility of this biochemicaldefect must obviously be considered in patientscomplaining of vague pains in the limb muscles,particularly after exertion, for which no neuro-logical, vascular or recognized cause can be found.The measurement of the blood lactate level beforeand after ischaemic exercise (McArdle, 1951) hasproved to be an extremely useful screening test,and if this is suggestive, the diagnosis should beproved by muscle biopsy with a histochemicaldemonstration of a reduction or absence of phos-phorylase activity. The latter is particularly im-portant as a similar picture with a failure of theblood lactate to rise after ischaemic exercise maybe produced by the absence of other enzymesinvolved in glycogen breakdown (Oliner, Schul-man & Larner, 1961).Treatment is at present unsatisfactory, and now

that the biochemical defect has been clearlydefined it is to be hoped that a method of itscircumvention will be discovered in the not toodistant future.

SummaryThe features of McArdle's syndrome have been

briefly reviewed, and four further cases reported,one being only partially affected. The variations inpresentation and clinical course, and the possible

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relation of the biochemical defect to epilepticseizures are discussed.

AcknowledgmentsI would like to thank the many people who helped in this

investigation, unfortunately too numerous to acknowledgeindividually. The patients were admitted under the care ofDr D. G. Adamson, and the muscle biopsy studies wereperformed by Dr G. W. Pearce.

ReferencesEHLERS, K.H. & ENGLE, M.A. (1963) Glycogen storage

disease of myocardium. Amer. Heart J. 65, 145.ENGEL, W.K., EYERMAN, E.L. & WILLIAMS, H.E. (1963)

Late-onset type of skeletal muscle phosphorylase de-ficiency. New Engl. J. Med. 268, 135.

HOCKADAY, T.D.R., DOWNEY, J.A. & MOTTRAM, R.F. (1964)A case of McArdle's Syndrome with a positive familyhistory. J. Neurol. Neurosurg. Psychiat. 27, 186.

MAHLER, R.F. (1966) Enzyme errors in the glycogen storagediseases. Second Symposium of Advanced Medicine.Pitman, London.

McARDLE, B. (1951) Myopathy due to a defect in muscleglycogen breakdown. Clin. Sci. 10, 13.

MELLICK, R.S., MAHLER, R.F. & HUGHES, B.P. (1962)McArdle's Syndrome. Phosphorylase-deficient myopathy.Lancet, i, 1045.

MOMMAERTS, W.F.H.M., ILLINGWORTH, B., PEARSON, C.M.,GUILLORY, R.J. & SERAYDARIAN, K. (1959) A functionaldisorder of muscle associated with the absence of phos-phorylase. Proc. nat. Acad. Sci. (Wash.), 45, 791.

OLINER, L., SCHULMAN, M. & LARNER, J. (1961) Myopathyassociated with glycogen deposition resulting fromgeneralised lack of amylo 1-6 glucosidase. Clin. Res. 9,243.

PEARCE, G.W. (1965) Histopathology of voluntary muscle.Postgrad. med. J. 41, 294.

PEARSON, C.M., RIMER, D.G. & MOMMAERTS, W.F.H.M.(1961) A metabolic myopathy due to absence of musclephosphorylase. Amer. J. Med. 30, 502.

RATINOV, G., BAKER, W.P. & SWAIMAN, K.F. (1965)McArdle's Syndrome with previously unreported electro-cardiographic and serum enzyme abnormalities. Ann.intern. Med. 62, 328.

ROWLAND, L.P., ARAKI, S. & CARMEL, P. (1965) Contracturein McArdle's Disease. Arch. Neurol. 13, 541.

ROWLAND, L.P., FAHN, S. & SCHOTLAND, D.L. (1963)McArdle's Disease. Hereditary myopathy due to absenceof muscle phosphorylase. Arch. Neurol. 9, 325.

SALMON, S.E. & TURNER, C.E. (1965) McArdle's Diseasepresenting as convulsion and rhabdomyolysis. Amer. J.Med. 39, 142.

SCHMID, R. & HAMMAKER, L. (1961) Hereditary absence ofmuscle phosphorylase (McArdle's Syndrome). NewEngi. J. Med. 264, 223.

SCHMID, R. & MAHLER, R. (1959) Chronic progressivemyopathy: Demonstration of a glycogenolytic defect inthe muscle. J. clin. Invest. 38, 2044.

SCHOTLAND, D.L., SPIRO, D., CARMEL, P. & ROWLAND, L.P.(1966) Ultrastructural studies of muscle in McArdle'sDisease. J. Neuropath. exp. Neurol. 25, 146.

TOBIN, R.B. -& COLEMAN, W.A. (1965) A family study ofphosphorylase deficiency in muscle. Ann. intern. Med. 62,313. copyright.

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