Andersons pediatric cardiology 1570

muscularatrophy(spinalmuscularatrophytype1,Werdnig-Hoffmandisease)is
alethalvariantpresentingwithseverehypotoniaandrespiratoryfailure.Various
congenitalheartdefectshavebeenreportedinpatientswiththisdisease,but
thesearelikelychanceassociations.289,290

RefsumDisease
Refsumdiseaseisarareneurologicdisorderduetotheaccumulationofphytanic
acidinperoxisomes.Phytanicacidisabranched-chainfattyacidthatispartially
brokendownbyphytanoyl-CoA2-hydroxylase,andmanycasesofthedisease
areduetodefectsinthegeneencodingthisenzyme.291Thisleadstothe
accumulationofphytanicacidinbloodandtissues.Symptomsappearinthefirst
andseconddecadesoflife,andtheinitialpresentationiswithweakness,
unsteadygait,andnightblindness.Thesepatientshaveadiagnostictetrad:
retinitispigmentosa,peripheralpolyneuropathywithdiminishedorabsentdeep
tendonreflexes,cerebellarataxia,andhighproteinlevelsincerebrospinalfluid
withoutpleocytosis.Otherfrequentsignsarenervedeafness,anosmia,
nystagmus,andabnormalitiesofthepupils.Theheartisrarelyaffected.
Conductionabnormalities,especiallyadvanceddegreesofatrioventricularblock
requiringpacemakertherapy,arewellknown.Cardiomyopathyisarare
association.292
Dietslowinphytanicacidproduceclinicalimprovement.Completerecovery
israrelyobtained,buttreatmentwillslowprogressionofthedisease.The
associationofplasmapheresiswiththedietreducesthelevelsofphytanicacid
morerapidly.293


NutritionalDeficiencies
Selenium
Seleniumisatraceelementthatisanessentialcomponentofglutathione
peroxidase.Theenzymeremovesorganichydroperoxidesfromthecell.Absence
ofselenium,possiblyassociatedwithabsenceofvitaminE,permitsdamageto

thecellmembranebylipidperoxides.Deficiencyofselenium,alsoknownas
Keshandisease,affectschildrenlivinginareaswithapoorcontentofselenium
inthesoilorthosereceivingapoordiet.294Itgivesrisetoanendemicdilated
cardiomyopathythataffectschildrenbetween1and9yearsofagelivinginan
areaextendingfromthenortheasttothesouthwestofChina,wherethecontent
ofseleniuminthesoilandfoodisverylow.Ithasalsobeenreportedwith
nutritionalchangesrelatedtobariatricsurgery295andwithtotalparenteral
nutrition.296ECGabnormalities—includingprematureventricularcontractions,
QRSwidening,andQTprolongation—inasymptomaticpatientsmaypredict
thoseatriskfordevelopingchronicKeshandisease.297Theincidencehasbeen
significantlyreducedbyaddingoralsodiumseleniteinthediet,withnoadverse
sideeffects.Oncefullydeveloped,thecardiomyopathyisirreversible298;
however,earlyrecognitionofthecauseofthecardiomyopathy,withtimely
institutionofseleniumsupplementation,canbringaboutresolution.299
Histopathologicfeaturesoftheheartareareasofmyocyticlosswithreplacement
fibrosisinthesubepicardialsurfacesoftheventricles.300

Carnitine
L-carnitine,orhydroxy-trimethylammoniumbutyrate,isanessentialcofactorin

thetransferoflong-chainfattyacidsacrosstheinnermitochondrialmembrane.
Depletionofcarnitineblocksthemitochondrialoxidationoffattyacidsandleads
tothecytoplasmicaccumulationoflipids.Cardiacandskeletalmusclesusefatty
acidsastheirmainsubstrateandthereforeareverysensitivetocarnitine.301
Primarysyndromesduetodeficiencyofcarnitinearedividedintomyopathicand
systemicforms.Patientswithmusculardeficiencypresentwithprogressive
weaknessandarethoughttohaveabnormaltransportofcarnitineintoskeletal
muscle.Theyhavenormallevelsofcarnitineintheplasmabutlow

concentrationsinthemuscles.Hypothesesforthecauseofsystemicdeficiency
includedefectsinsynthesis,renalhandling,gastrointestinalabsorptionand
cellulartransport,andexcessivedegradation.Atleastsomecaseshavebeen
demonstratedtobeduetodefectsinthecarnitinetransportergene.302
Accumulationoftriglyceridesinmuscleoftenoccurs,sincefattyacidsarenot
transportedeffectivelyintothemitochondriaforoxidation.Patientsoftenhave
lowconcentrationsofcarnitineintheplasmaandtissues,althoughthisisnota
sensitivemarkerforthedisease.Abouthalfofthepatientswithsystemic
primarycarnitinedeficiencypresentbefore2.5yearsofagewithametabolic
hepaticdisordercharacterizedbyencephalopathy,hypoglycemia,andliver
dysfunction.Thepresentationisoftenprecededbyfastingorarespiratory
illness.Theremainingpatientspresentataslightlyolderage,typicallyaround
age4,withamyopathic(cardiac)disordercharacterizedbyadilated
cardiomyopathyandhypotonia.Rarely,patientsarenotrecognizeduntil
adulthood.303
Cardiomyopathyhasfrequentlybeenreportedinassociationwitheither
systemicormyopathicdeficiency.Manypatientsareincardiacfailurewhenthey
cometomedicalattention.304TheECGisnonspecific,withsignsofleft
ventricularhypertrophy.VerytallandpeakedTwaves,likethoseseenin
hyperkalemia,havebeendescribed.305Theechocardiogramrevealsleft
ventricularandleftatrialdilationwithsignsofpoorleftventricularfunction.
Thelastcanalsobedemonstratedbynuclearangiography.Cardiacfailure
respondspoorlytoconventionaltherapy.Endocardialfibroelastosisasaresultof
systemicdeficiencyhasbeendescribed.306Thediagnosisisdependentonthe
demonstrationoflowlevelsofcarnitineinthetissuesorblood,althoughnormal
levelsdonotruleoutthedisorder.Musclebiopsyshowslargeamountsoflipids
intypeImusclefibersandabnormalmitochondria.Thediseaseisusuallyfatal
withouttreatment.OralL-carnitineproducesclinicalimprovementinmany
patients.307Othersfailtorespondtotherapy.308Diarrheaisthemainsideeffect.
Dietswithonly20%ofcaloriesfromfatarealsousefulinlong-termtreatment.

Carnitinedeficiencyisinheritedinautosomalrecessivefashion.

Thiamine(Beriberi)
Thiamine,orvitaminB1,isawater-solublevitaminthatisabsorbedfromthe
smallintestine.Initsactiveformofthiaminepyrophosphate,itisanessential