Andersons pediatric cardiology 1553

youngadultswiththeautosomalrecessiveformofthedisease.Rareformsof
phosphorylasebkinasedeficiencyhavebeendescribed,inwhichdepositionof
glycogenislimitedtotheheart.26

GlycogenStorageDiseaseTypeVII(Tarui
Disease,MusclePhosphofructokinaseI
Deficiency)
Taruidiseaseisarareformofglycogenstoragediseasethatpresentsinearly
childhoodoradultlifewithfatigability,muscularweakness,whichcanbe
progressive,musclecramps,andmyoglobinuria.Typicallytheheartisspared.
However,aninfantileformofthediseasehasbeendescribedinthemembersof
onefamily.Cardiomyopathyoccurredinadditiontotheprogressivemuscular
weakness,andabnormaldepositionofglycogenwasnotedinthecardiacmuscle
atautopsy.27Progressivecardiomyopathyhasalsobeenreportedinanadult.28

Mucopolysaccharidoses
Themucopolysaccharidosesresultfromdeficiencyoflysosomalenzymes
involvedinthedegradationofmucopolysaccharides.Theincompletelydegraded
mucopolysaccharidesthenaccumulateinthetissues.Thesubstances
accumulatedaredermatansulfate,heparansulfate,orkeratansulfate.Theycan
accumulatealoneorincombination.Thereisskeletalinvolvementinallforms.
Inmost,thereisglaucomaandcornealclouding.Retinalpigmentationfrequently
occurs.Deafnessisafeatureofalltypes.Inmost,thereishepatosplenomegaly.
Involvementofthecentralnervoussystemiscommon,usuallywithcervical
myelopathyasaconsequenceofpachymeningitisoratlanto-occipital
subluxation.
Cardiovascularinvolvementisafeatureofalltypes.The
mucopolysaccharidesaredepositedinarterialwalls,includingthecoronary
arteries,producinglesionssimilartoatherosclerosis.29Adilatedaorticrootis
alsofrequentlyseen.30Depositionincardiacvalvesleadstovalvarstenosis
and/orregurgitation.Thevariousformsofthesediseasesarebroughtaboutby

deficienciesof10identifiablelysosomalenzymes.Specificdeficienciescanbe
demonstratedinculturedfibroblasts,andprenataldiagnosisfromcultureof
amniocytesispossible.Theavailabilityofsuchdiagnosisisimportant,since


thereisgeneticvariabilitywithindifferentformsofmucopolysaccharidoses.

MucopolysaccharidosisTypeI(α-L-Iduronidase
Deficiency)
Thethreemajorclinicalformsofα-L-iduronidasedeficiencyareHurler
syndrome,Scheiesyndrome,andasyndromeintermediatebetweenthetwo,
Hurler-Scheiesyndrome.Thesediseasesareduetodefectsinthegeneencoding
α-L-iduronidase,andmultipledefectshavebeenelucidated.Theseinclude
nonsense,missense,insertional,deletional,andsplice-typegenedefects.Itwas
previouslythoughtthattheclinicalseverityofthediseasewasrelatedtothe
levelofdenovoenzymeactivity,butnobiochemicaldifferenceshavebeen
identifiedtodistinguishthesubtypes.31–33
HurlerSyndrome.
ThedefectinHurlersyndromeresultsinavirtualabsenceoflysosomalα-Liduronidase.Thisenzymeisresponsibleforthebreakdownofheparansulfate
anddermatansulfatetoheparanandhyaluronicacid,respectively.Theenzymeis
completelyabsentinfibroblastsbutsomeactivityispresentintheliver.
Consequentlytracesofthebreakdownproductsofheparananddermatanmaybe
foundintheurine.Asaconsequenceofthisenzymedeficiency,bothheparan
anddermatansulfatesaccumulateinthelysosomesofmanytissues.Whenin
neurons,thelesionsbearsomeresemblancetothosefoundinTay-Sachsdisease.
Depositioninthearterialwallsisassociatedwithproliferationofsmoothmuscle
cells,andthelesionsaredescribedas“pseudoatheromatous.”Thereis
proliferationofbothelasticfibersandcollagenaccompanyingthelysosomal
accumulationofmucopolysaccharides.
Thebabiesseemtobenormalatbirth,theclinicalfeaturesappearingafterthe

ageof1year,whenthefacialfeaturesbecomecoarse.Prematureclosureofthe
skullsuturesandhydrocephalusasaconsequenceofpachymeningitisleadto
cranialdeformities.Thecharacteristiclumbarlordosisdevelopsbecauseofstiff
joints.Growthretardationthenbecomesevidentaftertheageof2or3years;
deafness,cornealclouding,and(sometimes)glaucomasubsequentlydevelop.
Theliverandspleenarealwaysenlarged.Althoughtheheartisrarelyspared,
clinicalevidenceofcardiacinvolvementisseenonlyinhalfthepatients.Angina
pectorisisanoccasionalsymptombecauseofcoronaryarteryinvolvement,but
morefrequentlyattentionisdrawnbythefindingofacardiacmurmuror


systemichypertension.Themurmursarevariableandusuallynotloud.Rarely,
themurmurofaorticormitralinsufficiencymaybeheard.Cardiacfailureasthe
presentingfeatureassociatedwithendocardialfibroelastosishasbeen
reported.34,35
Therearetypicalskeletalradiologicfeatures.Theclavicleshavewidemedial
ends.Thelowerthoracicandupperlumbarvertebraehaveaflaredandhookshapedappearance.Therearealsochangesintheskullandlongbones,thelatter
beingmoreseverelyaffectedintheupperlimbs.Theheartisusuallyenlarged
butwithnospecificsilhouette,althoughleftatrialenlargementwilloccurwith
severemitralregurgitation.Similarly,therearenospecificelectrocardiographic
features,althoughcombinedventricularhypertrophyisfrequent.AlongQT
intervalhasbeenreportedinsomepatients.36
Pathologicfindingsintheheartincludedepositionofmucopolysaccharidein
structuressuchasthesinusandatrioventricularnodesaswellasinthe
myocardiumandendocardium.Thecoronaryarteriesoftendemonstratesevere
luminalnarrowing,andcaremustbetakenwheneverthesepatientsaresubjected
togeneralanesthesiaorsedation,ashypotensioncanleadtocoronaryischemia
anddeath.Themitralvalveismostfrequentlyinvolved,followedbytheaortic
andtricuspidvalves.Pulmonaryvalveinvolvementisonlyrarelyreported.
Valvarchangesincludenodularthickeningalongthefreeedges,whichmaylead

tostenosisorregurgitation.Evidencesuggeststhattheaccumulationofdermatan
sulfateleadstoimpairedelastogenesis,whichmayleadtosomeofthe
characteristicarterialandvalvardeformities.37
Thickeningofthevalveleafletsischaracteristicallyseen
echocardiographically.Leftventricularcavityenlargementwillreflectthe
volumeloadresultingfromvalvarregurgitation,andleftventricularmassmay
beincreasedasaresultofcompensatoryhypertrophyanddepositionof
mucopolysaccharideinthemyocardium.Cardiaccatheterizationand
angiocardiographyaddlittletothediagnosticfindings,whichincludesystemic
andmildpulmonaryhypertension.Ifangiographyisperformed,the
hemodynamicswillreflecttheseverityofvalvarinsufficiency.Thedisease
progressesinexorably,deathoccurringbytheageof10yearsfromheartfailure,
suddendeath,orfromchestinfection.Hematopoieticstemcelltransplantation
hasbeenbeneficialinselectedpatientsformanyaspectsofthedisease.38
However,thevalvarlesionsremainprogressive.Enzymereplacementtherapy
withhumanrecombinantα-L-iduronidasehasalsoprovedbeneficial,but,aswith
stemcelltransplantation,thevalvarlesionsappeartoremainandeven