Andersons pediatric cardiology 1551

Abstract
Cardiacinvolvementinsystemicdiseasecanbebroadlydividedintothose
conditionswheretheheartisinvolvedinthediseaseprocessitselfandthose
whereastructuralorfunctionalcardiacabnormalityisassociatedwithother
anomalies,usuallyinarecognizablesyndrome.Manyoftheconditionsin
thelattergrouphavereceivedattentioninthesectionsofthisbookdealing
withetiologyandgenetics.Theyarenotdealtwithinthischapter,although
theymaybementioned,orthediscussionamplified,asnecessary.Avast
numberofsystemicdiseases,nonetheless,caninvolvetheheartduring
childhood.Cardiacaspectsofthelatterdiseasesarethefocusofthis
chapter.

Keywords
Cardiomyopathy;metabolic;neuromuscular;collagensynthesis;
endocrine;energymetabolism;nutritionalautoimmunedisorders
Cardiacinvolvementinsystemicdiseasecanbroadlybedividedintothose
conditionswheretheheartisinvolvedinthediseaseprocessitselfandthose
whereastructuralorfunctionalcardiacabnormalityisassociatedwithother
anomalies,usuallyinarecognizablesyndrome.Manyoftheconditionsinthe
lattergrouphavereceivedattentioninthesectionsofthisbookdealingwith
etiologyandgenetics.Theyarenotdealtwithagainhere,althoughtheymaybe
mentionedorthediscussionamplifiedasnecessary.Avastnumberofsystemic
diseases,nonetheless,caninvolvetheheartduringchildhood.Cardiacaspectsof
thelatterdiseasesarethefocusofthischapter.


MetabolicDisorders:StorageDiseases
GlycogenStorageDiseases
GlycogenStorageDiseaseTypeI(VonGierke
Disease,Glucose6-PhosphataseDeficiency
[TypeIa],Glucose6-PhosphataseTranslocase

Deficiency[TypeIb])
VonGierkediseaseisanautosomalrecessivedisorder.Clinicalmanifestationsof
typeIglycogenstoragediseaseareprofoundhypoglycemiaassociatedwith
hyperlipidemia,hyperuricemia,andlacticacidosis.Itpresentsinchildhoodand
primarilyinvolvestheliver,kidneys,andsmallintestinalmucosa.Pulmonary
hypertensioninassociationwithtypeIaglycogenstoragediseasehasbeen
described;whenpresent,theprognosisisverypoor.Postulatedmechanisms
includechronicstimulationofthesmoothmuscleofthepulmonaryarteriolesby
thepersistenthepaticmetabolismofcirculatingcatecholaminessuchas
serotonin.Indeed,serotoninlevelshavebeenshowntobemarkedlyelevatedin
somepatientswithglycogenstoragediseasetypeI.However,elevatedserotonin
levelsalonedonotappeartoconferpulmonaryvasculardiseaseonthese
patients.Rather,itishypothesizedthatothermediatingfactorsinconcertwith
persistentlyelevatedserotoninlevelsincreasetheriskforpulmonaryvascular
changes.Genetherapiesarebeingdevelopedtotreatglycogenstoragedisease
typeIandinitialresultsappearpromising.1–3

GlycogenStorageDiseaseTypeII(Pompe
Disease)
Pompediseaseisageneralizedglycogenstoragediseaseinwhichglycogenof
normalstructureaccumulatesinthemyocardium,skeletalmuscle,andliver.The
diseaseisprogressiveandisassociatedwithdeficiencyoflysosomalα-1,4glucosidase.Therearefoursubtypesbasedonageatonsetofclinicalsymptoms:
infantile(classicPompedisease),childhood,juvenile,andadult.Theageat
onsetcorrelatesinverselywiththemeasuredactivityoflysosomalα-1,4glucosidaseinmusclecellsorfibroblasts.Intheinfantileform,whichgenerally


hasmoreseverecardiacinvolvementthantheformswithlateronset,thereis
generalizedaccumulationofglycogenintheheart(includingintheconduction
tissues),inskeletalmuscle(notablythetongueanddiaphragm),andintheliver.
Centralandperipheralneuronsandsmoothmusclearealsoaffected.Theresults

arecardiomegaly,hepatomegaly,athickeneddiaphragm,andmacroglossia.In
theheart,theglycogenisdepositedmainlyinventricularmuscle.Thereisgross
thickeningoftheventricularwalls,withimpairmentofbothdiastolicand
systolicperformance.Theinfantstypicallyappearnormalatbirth,although
casesofsevereneonatalventricularhypertrophyhavebeenreported.4The
medianageatonsetofclinicalsymptomsis1.6months.Muscleweaknessand
hypotoniaalongwithlossofmotormilestonesarenotedduringthefirst6
monthsoflife,andsignsofCHFbecomeevident.Althoughthereisexcess
glycogenintheliver,hepatomegalyisnotcommonlypresentuntilheartfailure
isapparent.Thediseaseisprogressive,andmostaffectedbabiesdiebeforethe
ageof1year.Theclinicalcoursemaybecomplicatedbyarrhythmias.Since
patientswithPompediseaseappearverysensitivetodigoxin,thisdrugmustbe
usedwithextremecaution.Irritabilityandpoorfeedingoftendrawattentionto
thedisease.Thecardiacphysicalsignsarenotcharacteristic,withvariable
murmursbeingheard.UnexplainedcardiomegalyandCHFinagenerally
“floppy”babyshouldsuggestthediagnosis.5
Thechestradiographmaybenormalatbirth,butinallaffectedinfantsthe
heartbecomesenlargedwithinafewweeks.Thereisnospecificpatterntothe
cardiacsilhouettebutratherageneralizedsmoothenlargementofthecontour.
ThecharacteristicelectrocardiographicfeaturesareashortPRinterval,wider
thannormalQRScomplexes,andvoltageevidenceofleftorbiventricular
hypertrophy,whichcanbesevere(Fig.59.1).Inaddition,inthemajoritythere
areQwavesandinvertedTwavesinleadsI,II,andtheleftchestleads.6
ElectrophysiologicstudieshaveshownashortA-Hinterval.7BothM-modeand
cross-sectionalechocardiographydemonstrategrossincreaseinthethicknessof
theventricularfreewallsandtheventricularseptum(Fig.59.2).Impaired
diastolicfillingisfrequent,8togetherwithreductionoftherateandextentof
systolicshortening.Cardiaccatheterizationisrarelyperformedasitaddslittleto
thediagnosisormanagement.