Andersons pediatric cardiology 1571

coenzymeinthemetabolismofpyruvateandinthetransketolasereaction.
Deficiencyproducesadiseaseknownasberiberi,whichhasbeenrelatedtodiets
consistingofpolishedriceinAsiansocietiesandtoalcoholismintheOccident.
Classically,thediseasehasbeendividedintotwomajortypes.Indryberiberi,
thepatientshaveperipheralneuropathywithvarieddisordersofsensation,
sometimesamountingtoanesthesia,muscleweaknessandatrophy,reduceddeep
tendonreflexes,fatigue,anddifficultyconcentrating.Incontrast,inwetberiberi,
wherethepresentingfeaturesareahigh-outputcardiacfailurewithperipheral
edema,thepatientshavediminishedperipheralvascularresistanceasaresultof
musculararteriolarvasodilation,awidepulsepressure,andawarmskin.The
mechanismleadingtoareductionofperipheralvascularresistanceisbelievedto
bedirectlyrelatedtothelackofthiamine,sinceaftertreatmentthisparameter
returnsrapidlytonormal.309Despitethehighcardiacoutput,oliguriaispresent
owingtoreductionofrenalbloodflowandglomerularfiltrationrate.Increased
jugularvenouspressureresultsfromperipheralvenoconstrictionandanincrease
inthecirculatingbloodvolume.310Cutaneousvasoconstrictionbecomesevident
withtheprogressionofcardiacfailure,whichresultsincoldhandsand
peripheralcyanosis.Itisnotclearwhetherthecardiacfailureresultsfrom
primarymyocardialinvolvementorwhetheritissecondarytothevascular
changes.Insomepatientstheadditionaltoxiceffectsofalcoholmakethis
differentiationverydifficult.Histologicstudiesofthehearthaveshownhydropic
degeneration,interstitialandperivascularedema,andfibrosisandnecrosisof
myocardialtissue.311
Anacutevariantofthediseasewithvascularcollapse,metabolicacidosis,and
variablecardiacoutputisknownasshoshinberiberi.Patientspresentinsevere
biventricularfailure.Theyhaverenaldysfunctionleadingtometabolicacidosis.
Thereisahigharterialsaturationofoxygensecondarytotachypnea,which
contrastswiththeperipheralcyanosiscausedbycutaneousvasoconstriction.312
Cardiaccatheterizationrevealsincreasedrightandleftatrialpressuresandalow
peripheralvascularresistance.313Earlydiagnosisisnecessarybecausepatients
dierapidlyifleftuntreated.Thepresentationvarieswithage.Affectedinfants

areveryrarelyseeninWesterncountries.Itappearsinnursingbabiesof
thiamine-deficientmothersaround1to4monthsofage.Sometimestheclinical
onsetissudden.AcuteCHFmaythenappearinapparentlyhealthybabies
followingaminorillness.Inothers,signsandsymptomsmimickingmeningitis
areseen.Administrationofthiamineproducesarapidrecovery.
Beyondinfancy,thedryformisseeninchildrenfedpolishedrice.Signsand


symptomsareofperipheralneuropathy.Cardiovascularinvolvementandedema
arerare.Whenthediseasepresentsinadolescence,alcoholconsumptionmustbe
consideredinadditiontopoordietaryintake.Patientsmanifestmalaise,fatigue,
palpitations,dyspnea,andperipheraledema.Theyhaveanincreasedjugular
venouspressure,ahighpulsepressure,agalloprhythmwithnonspecificapical
systolicmurmurs,andaloudpulmonarycomponenttothesecondheartsound.
Thereiscardiomegalyonthechestradiographinhalf,andtheECGshows
nonspecificT-wavechanges.Hemodynamicstudiesrevealahighcardiacindex,
strokeindex,andcirculatingbloodvolumeandlowperipheralvascular
resistance.
Clinicalsuspicionandadietaryhistoryofpoorthiamineintakeand/or
excessiveconsumptionofalcoholarenecessaryfordiagnosis.Patientswith
beriberiexhibitlowtransketolaseactivityinerythrocytes,whichincreasesafter
theadministrationofthiaminepyrophosphate.Patientshavelowlevelsof
thiamineintheirbloodandurine.Anacuteresponsetointravenousthiamine
duringcardiaccatheterization,withanincreaseinperipheralvascularresistance
andareductionincardiacoutput,hasalsobeenusedasadiagnostictest.314
Beriberiisatreatablecauseofcardiacfailure.Thereisarapidresponseto
administrationofthiamine.Parenteraltherapyisnecessaryinextremecases.
Administrationcanlaterbecontinuedorally.Bedrest,oxygen,diuretics,and
digitalisareusefultherapeuticadjuncts.Shoshinberiberiisamedicalemergency
thatisfatalwithoutaggressivemedicalmanagement.Correctionoftheacidosis

withsodiumbicarbonateisessential,togetherwiththemeasuresalready
described.Abalanceddiet—withanadequateintakeofmeat,freshvegetables
andwholegrains—willsupplythedailyrequirementsofthiamineandprevent
beriberi.


DepositionDiseases
Themajordiseasecausedbydisordereddepositionthatarisesinchildhoodis
hemochromatosis.Theotherdepositions,suchasamyloidosis,donotusually
manifestpriortoadulthood.

Hemochromatosis
Hemochromatosisresultsfromthedepositionofiron.Itmaybeprimaryand
hereditaryoritmaybesecondary.Primaryorhereditaryhemochromatosis
resultsfromtheexcessiveabsorptionofironfromthediet.Thenormalrateof
intestinalironabsorptionis1to2mg/day,butthiscanincreasewhennecessary.
Inpatientswithhemochromatosis,intestinalironabsorptioncanbeashighas8
to10mg/day.Also,mostironintheplasmaisstoredinmacrophages,andin
patientswithhemochromatosis,macrophagesmorereadilyreleasetheirstoresof
iron.Intestinalabsorptionandmacrophagereleaseareunderthecontrolof
hepcidin,anantimicrobialpeptidesynthesizedbytheliver.Hepcidinactsto
downregulateabsorptionandreleasethroughitsdegradationofferroportin,a
membraneproteincriticalfortheuptakeandreleaseofiron.Synthesisof
hepcidinisregulatedbymultipleproteinsinresponsetotheneedforand
availabilityofiron.Thusdefectsinvolvingthehepcidingene,thegenes
encodingitsregulatorproteins,ortheferroportingenecanallpromotethe
excessiveuptakeandreleaseofiron,leadingtodepositionintheorgans.These
disordersareinheritedinanautosomalrecessivefashion.Thespecificgene
affecteddeterminestheclinicalphenotype.315
Secondaryhemochromatosisisgenerallytheresultofexcessive

administrationofironthroughmultiplebloodtransfusionsinchronic
transfusion-dependentnonhemorrhagicanemias.Themostfrequentoftheseisβthalassemia.Each250mLofblooddeliversapproximately200mgofiron.316
Cardiacdysfunctiongenerallyoccursafter100unitsofbloodhavebeen
transfused.317Althoughtheprimaryandsecondarydiseasesarequitedifferent,
thedamagingeffectsofironaresimilar.Theexcessironinthetissuesweakens
thelysosomalmembranesandproducesdamagetothecells.
Damagetoorgansduetoprimaryhemochromatosisgenerallyappears
between40and60yearsofage,althoughthosewiththemorerarejuvenileform
canexhibitsymptomsmuchearlier.Cardiacinvolvementoccursinoneinthree