Andersons pediatric cardiology 1552

FIG.59.1 TypicalelectrocardiogramofapatientwithPompedisease
demonstratesstrikingbiventricularhypertrophy.

FIG.59.2 Typicalechocardiographicfindingsinglycogenstoragedisease
typeII.(A)Diastolicframeinlongaxisrevealssevereconcentricleft
ventricularhypertrophy,whilethesystolicframefromthesamechild(B)
showstheabsenceofsubaorticobstruction.


Thecompleteclinicalpicturetogetherwiththecharacteristic
electrocardiographicandechocardiographicfindingswillleadimmediatelyto
thedefinitivediagnosticinvestigation.Thisisthedemonstrationofdeficiencyof
lysosomalα-1,4-glucosidaseinfibroblastsgrownfromaskinbiopsy.Sometimes
theskeletalmuscleabnormalitiesarelessevident.Thepresentationisthenasa
cardiomyopathyalone.Pompediseaseshouldbeconsideredinanysuchcaseand
skinbiopsyperformed.Untilrecentlytherewasnospecifictreatmentavailable,
andsupportiveanddecongestivemeasuresfailedtoimproveoutcomes.
However,recentstudiesusingrecombinanthumanlysosomalacidα-glucosidase
showpromiseinimprovingsurvival.9Earlydiagnosis,typicallyviastandardized
newbornscreeningindevelopedcountries,andearlyinitiationofenzyme
replacementtherapyshowsthemostbenefit.10Sincethediseaseappearstobe
inheritedinanautosomalrecessivefashion,parentsshouldbeadvisedofthe
availabilityofprenataldiagnosisviacultureofamniocytesobtainedby
amniocentesis.
Danondiseaseisincludedinthissectionbecauseitwaspreviouslyconsidered
tobeavariantofPompediseaseknownasglycogenstoragediseasetypeIIb,
withnormalacidmaltase.Thediseaseisduetoadeficiencyoflysosomeassociatedprotein2(lamp-2)andmanifestsasaprogressivehypertrophic
cardiomyopathywithskeletalmyopathy.Othersimilardiseasesinthisfamilyof
autophagicvacuolarmyopathiesarestillbeingstudied.Somedemonstrate
autosomalrecessiveinheritance,whereasothersarex-linked,andthedegreeof
cardiacandskeletalinvolvementisvariable.11

GlycogenStorageDiseaseTypeIII(CoriDisease,
Amylo-1,6-Glucosidase[Debrancher]Deficiency)
InCoridisease,anautosomalrecessivecondition,glycogenaccumulatesin
skeletalmuscle,theliver,andcardiacmuscleduetoadeficiencyofamylo-1,6glucosidase,theenzymenecessaryforbreakingdownbranchpointsinglycogen
chains.Therearethreesubtypes,whicharedependentontheprimarysiteof
abnormalglycogenstorage(IIIa,liverandmuscle;IIIb,liver;IIIc,muscle).12A
fourthsubtype(IIId)involvesnormaldebrancherenzymeactivitybuta
deficiencyofdebrancherenzymetransferaseactivity.13PatientswithtypesIIIa
andchaveatendencytodevelopskeletalmuscleweaknessandleftventricular
hypertrophy,14whichisprogressive.Astudyfoundthat58%ofpatientswith


glycogenstoragediseaseIIIahadsomedegreeofventricularhypertrophy.15
However,theclinicalcourseappearstobelesssevere,withfewersymptoms,as
comparedwithhypertrophicobstructivecardiomyopathy.16,17

GlycogenStorageDiseaseTypeIV(Andersen
Disease,α-1,4-Glucan-6-Glucosyltransferase
[Brancher]Deficiency)
Andersendiseaseisarareheterogeneousglycogenstoragediseasecharacterized
bythedepositionofglycogenofabnormalstructureintheliver,leadingto
cirrhosis.Theremayalsobedepositionofglycogenintheheart.Consequently,
althoughliverdysfunctionisthemostcommonclinicalmanifestation,the
diseasecanrarelypresentwithdilatedcardiomyopathy,whichistypically
severe.18–21

GlycogenStorageDiseaseTypeV(McArdle
Disease,MusclePhosphorylaseDeficiency)
McArdlediseaseisanautosomalrecessiveconditionthatresultsfroma

deficiencyofmuscleglycogenphosphorylase.Itisoftennotdiagnoseduntil
adolescenceoradultlifeandiscommonlymisdiagnosedinchildhood.22Itsmain
clinicalfeaturesaremusclefatigability,musclecramps,andmyoglobinuria.Rare
lethalvariantshavebeenreportedininfants,23buttheheartistypicallyspared.
Thismaybeduetoactivityofadistinctcardiacphosphorylaseisozymethat
retainsactivityinpatientswithdeficiencyoftheskeletalisozyme.24Noclinical
cardiacmanifestationshavebeenreported,butonoccasionthe
electrocardiogram(ECG)hasfeaturessimilartothoseseeninPompedisease.25

GlycogenStorageDiseaseTypeVI(Hers
Disease,PhosphorylaseBKinaseDeficiency,or
LiverPhosphorylaseDeficiency)
Hersdiseaseinvolvesbothx-linkedandautosomalrecessivemodesof
inheritanceandresultsfromdeficiencyofliverphosphorylase.Bothhave
involvementoftheliverinchildhood,whereasinvolvementofmusclesoccursin