fenotipo acidurias

7/25/2019 fenotipo acidurias

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Journal of Inherited Metabolic DiseaseOcial Journal of the Society for the Study of Inborn Errors ofMetabolism

SSIEM 201510100!"s105#5$015$%&'%$'

Ori(inal )rticle

The phenotypic spectrum of organicacidurias and urea cycle disorders. Part 1:the initial presentationStefan *+l,er1 -)n(eles .arcia /aorla 2- assili alayannooulos'- )llan M 3und#- )lberto 44urlina5-Jolanta Sy,ut$/e(iels,a- 6rits ) 7i8bur(!- Elisa 3e9o :eles&- Jiri ;eman%- /arlo Dionisi$ici10- Iersehone )u(oustides$SaeGa$Huintana'1-Dani8ela >et,o


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L12/linic for >ediatrics I- Inherited Metabolic Disorders- Medical Nni


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SerFdiatriKue- /liniKues Nni


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ASL

)r(ininosuccinate lyaseASS

)r(ininosuccinate synthetaseCPS1

/arbamylhoshate synthetase 1E-HOD

Euroean netBor, and re(istry for homocystinurias and methylation defectsE-IMD

Euroean re(istry and netBor, for into?ication tye metabolic diseasesGA1

.lutaric aciduria tye 1HHH

yerornithinemia$hyerammonemia$homocitrullinuriaIVA

Isoroionic aciduriaQ

HuartileQoL

Huality of lifeUCD

Nrea cycle disorder

Introduction:he clinical resentation of atients Bith inherited or(anic acidurias LO)D and ureacycle disorders LN/D is


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Since O)D and N/D are rare diseases and most studies ha


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6or descritiSS LI4M S>SS Statistics 220 Bas used Standard de


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before the cut$o date for inclusion Lie 1 January 2011 >atients Bith late onset ofsymtoms shoBed more often and more ronounced dia(nostic delay than those Bithneonatal onset of symtoms L:able 1 7ithout aroriate metabolic treatment it isli,ely to assume that in both (rous an un,noBn number of atients died undia(nosed

Fig. 6reKuency of O)D and N/D in the E$IMD samle )bbreS1-carbamylhoshate synthetase 1Z D- de[ciencyZ .)1- (lutaric aciduria tye 1Z syndr- hyerornithinemia$hyerammonemia$homocitrullinuria syndromeZ I)- iso


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)symtomatic atients Bho Bere dia(nosed Bhile bein( asymtomatic Lby neBbornscreenin(- hi(h$ris, family screenin(- renatal testin( or symtomatic atients Bithincomlete clinical data LO)DY #0Z N/DY '# Bere e?cluded from this analysis)bbre


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atients- the mode of dia(nosis Bas not reorted ) detailed e


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iseasegroup

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disease L)S3 de[ciency- renal disease L)SS de[ciency and O)D renal disease L.)1-sychiatric disease LI)- re$eclamsia L>)- I)- eclamsia L.)1- and eilesy L>)/ardiac roblems Bere not reortede?t- Be studied Bhether there is eostnatal roblems Bere common in O)D Ln ] 111 and N/D Ln ] !2atients- Bith feedin( roblems LO)DY 20 ^- N/DY 1# ^ and hyerbilirubinemia LO)DY% ^- N/DY ! ^ bein( most freKuently reorted Some of these roblems Le( feedin(roblems most li,ely re`ect the be(innin( of a neonatal metabolic crisis- Bhereasothers Le( hyerbilirubinemia are found in the same ran(e as in the (eneraloulation )nthroometrical arameters Bere mostly in the normal ran(e- hoBe


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is

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Acute metabolic crisis ) clinical presentation and metabolicderangement

) metabolic crisis is an acute life$threatenin( e


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>atients Bith .)1 are e?cluded from this table- since they resent Bith anencehaloathic crisis but not Bith a classic metabolic crisis 6or descriti) atients shoBed astron(er decrease in standard bicarbonate and j less ronounced j in /O 2and L>) only than those Bith early$onset of symtoms L:able 5Z Sul :able 5 In the N/D(rou- early$onset male O:/ atients had a si(ni[cantly hi(her concentration ofammonia- (lutamine- ornithine- orotic acid and lactate- and a loBer concentration of

standard bicarbonate and citrulline than late$onset atients Similarly- symtomaticfemale O:/ carriers Bho had a neonatal metabolic crisis had a hi(her ammonia andtendency toBards hi(her lactate and loBer than those Bith late onset of symtoms)lthou(h early$onset atients Bith />S1- )SS and )S3 de[ciency also seemed to ha


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+hen does the disease start,

)ccumulation of to?ic metabolites in fetuses Bith O)D and N/D is usually thou(ht to bematernally re


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Since N/D atients resentin( Bith a neonatal metabolic crisis ha


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countries are increasin(ly included in neBborn screenin( ro(rammes in Euroe- andsome countries also screen for MM) Lisolated forms- n ] 1Z combined forms- n ] !- >)Ln ] !- )S3 Ln ] and )SS de[ciency Ln ] 5 L4ur(ard et al 2012Z 3oeber et al 2012eBborn screenin( for some N/D L).Sand />S1 de[ciency is technicallychallen(in(- and screenin( of female O:/ carriers results in a dia(nostic and ethicaldilemma E?cet for sin(le diseases such as .)1- there is still uncertainty Bhetheratients Bith O)D and N/D Bill bene[t from neBborn screenin( L*+l,er et al 2007Zerin(er et al 2010 :herefore- more Bor, is reKuired to understand Bhether neBbornscreenin( for MM)- >) and N/D imro


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anni(an L/3IM4- /hildren 3i


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Members of the Nrea /ycle Disorders /onsortium- 4atshaB M3- :uchman M- Summar M-

Seminara J L201# ) lon(itudinal study of urea cycle disorders Mol .enet Metab

11'Y12!1'0/ross@ef

4aum(artner M@- +rster 6- Dionisi$ici / et al L201# >roosed (uidelines for the

dia(nosis and mana(ement of methylmalonic and roionic acidemia Orhanet J @are

Dis %Y1'0/ross@ef>ubMed/entral>ubMed

4oy - ae(e .- erin(er J et al L201' 3oB lysine diet in (lutaric aciduria tye I j

eect on anthroometrical and biochemical folloB$u arameters J Inherit Metab Dis

'Y5255''/ross@ef>ubMed

4ur(ard >- @u *- 3indner M et al L2012 eBborn screenin( ro(rammes in EuroeZ

ar(uments and eorts re(ardin( harmoniation >art 2 6rom screenin( laboratory

results to treatment- folloB$u and Kuality assurance J Inherit Metab Dis '5Y1'

25/ross@ef>ubMed

/handler @J- ;erfas >M- Shans,e S- Sloan J- omann - DiMauro S- enditti /> L200%

Mitochondrial dysfunction in mut methylmalonic acidemia 6)SE4 J 2'Y1252

121/ross@ef>ubMed/entral >ubMed

/haman *)- .roman )- Mac3eod E et al L2012 )cute mana(ement of roionic

acidemia Mol .enet Metab 105Y125/ross@ef>ubMed/entral>ubMed

/ole :J L1%%0 :he 3MS method for constructin( normalied (roBth standards Eur J /lin

utr ##Y#50>ubMed

/ole :J- 6reeman J- >reece M) L1%%& 4ritish 1%%0 (roBth reference centiles for

Bei(ht- hei(ht- body mass inde? and head circumference [tted by ma?imum enalied

li,elihood Stat Med 1!Y#0!#2%/ross@ef>ubMed

/ole :J- 7illiams )6- 7ri(ht /M L2011 @eubMed

de *eyer p- alayannooulos - 4enoist J6 et al L200% Multile O>OS de[ciency in

the liediatr @es Y%1%5/ross@ef>ubMed
http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2014.08.001http://dx.doi.org.sci-hub.org/10.1186/s13023-014-0130-8http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4180313http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4180313http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=25205257http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9517-7http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22971958http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9484-zhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22544437http://dx.doi.org.sci-hub.org/10.1096/fj.08-121848http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC2660647http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC2660647http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19088183http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2011.09.026http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4133996http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4133996http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22000903http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=2354692http://dx.doi.org.sci-hub.org/10.1002/(SICI)1097-0258(19980228)17%3A4%3C407%3A%3AAID-SIM742%3E3.0.CO%3B2-Lhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9496720http://dx.doi.org.sci-hub.org/10.3109/03014460.2011.544139http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21175302http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2012.09.001http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23021068http://dx.doi.org.sci-hub.org/10.1203/PDR.0b013e3181a7c270http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19342984http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2014.08.001http://dx.doi.org.sci-hub.org/10.1186/s13023-014-0130-8http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4180313http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=25205257http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9517-7http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22971958http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9484-zhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22544437http://dx.doi.org.sci-hub.org/10.1096/fj.08-121848http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC2660647http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19088183http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2011.09.026http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4133996http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22000903http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=2354692http://dx.doi.org.sci-hub.org/10.1002/(SICI)1097-0258(19980228)17%3A4%3C407%3A%3AAID-SIM742%3E3.0.CO%3B2-Lhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9496720http://dx.doi.org.sci-hub.org/10.3109/03014460.2011.544139http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21175302http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2012.09.001http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23021068http://dx.doi.org.sci-hub.org/10.1203/PDR.0b013e3181a7c270http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19342984


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Dionisi$ici /- Deodato 6- @+schin(er 7- @head 7- 7ilc,en 4 L200 /lassical or(anic

acidurias- roionic aciduria- methylmalonic aciduria and isoubMed/entral>ubMed

Enns .M- 4erry S)- 4erry 4:- @head 7J- 4rusiloB S7- amosh ) L200! Surroionic acidemiaY clinical course and

outcome in 55 ediatric and adolescent atients Orhanet J @are Dis

&Y/ross@ef>ubMed/entral>ubMed

.utiFrre JunKuera /- 4almaseda E et al L200% )cute liubMed

berle J- 4urlina )- /ha,raani ) et al L2012 Su((ested (uidelines for the dia(nosis

and mana(ement of urea cycle disorders Orhanet J @are Dis

!Y'2/ross@ef>ubMed/entral >ubMed

artin( I- eumaier$>robst E- Seit ) et al L200% Dynamic chan(es of striatal and

e?trastriatal abnormalities in (lutaric aciduria tye I 4rain 1'2Y1!#

1!&2/ross@ef>ubMed

erin(er J- 4oy S>- Ensenauer @ et al L2010 Nse of (uidelines imro


31/69

omann .6- )thanassooulos S- 4urlina )4 et al L1%% /linical course- early

dia(nosis- treatment- and reubMed

*ido J- a,amura *- Mitsubuchi et al L2012 3on($term outcome and interediatr @es 52Y1%%20/ross@ef>ubMed

*+l,er S- .arbade S6- .reenber( /@ et al L200 atural history- outcome- and

theraeutic ecacy in children and adults Bith (lutaryl$/o) dehydro(enase de[ciency

>ediatr @es 5%Y!/ross@ef>ubMed

*+l,er S- .arbade S6- 4oy et al L200! Decline of acute encehaloathic crises in

children Bith (lutaryl$/o) dehydro(enase de[ciency identi[ed by neBborn screenin( in

.ermany >ediatr @es 2Y'5!'2/ross@ef>ubMed

*+l,er S- /hristensen E- 3eonard J et al L2011 Dia(nosis and mana(ement of (lutaric

aciduria tye I j reubMed

*+l,er S- Dobbelaere D- berle J et al L2015 etBor,in( across borders for indiubMed/entral>ubMed

3eonard J- i8ayara(ha


32/69

3iu J- .alla(her )E- /arta /M- :orres ME- Moran @- 7ilco? S L201# @acial dierences in

(estational Bei(ht (ain and re(nancy$related hyertension )nn Eidemiol 2#Y##1

##!/ross@ef>ubMed

3oeber J.- 4ur(ard >- /ornel M/ et al L2012 eBborn screenin( ro(rammes in

EuroeZ ar(uments and eorts re(ardin( harmoniation >art 1 6rom blood sot to

screenin( result J Inherit Metab Dis '5Y0'11/ross@ef>ubMed

Mc/lelland M- 4a,alino L200% .lutaric aciduria tye 1

resentin( Bith eilesy De< Med /hild eurol 51Y2'52'%/ross@ef>ubMed

Mustafa )- /lar,e J: L200 Ornithine transcarbamylase de[ciency resentin( Bith

acute liubMed

asso(ne M/- Fron 4- :ouati .- @abier D- Saudubray JM L2005 Nrea cycle defectsY

mana(ement and outcome J Inherit Metab Dis 2&Y#0!#1#/ross@ef>ubMed

ettesheim S- berle J- *arall D et al L201' eu dia(nostiierte

arnstoy,lusdefe,te bei >atienten unter 1 Jahren Monatsschr *inderheil,d

11LSul 2Y1- abstract

O,un J.- +rster 6- 6ar,as 3M et al L2002 eurode(eneration in methylmalonic

aciduria in- S,oubMed

>ena 3- 6ran,s J- /haman *) et al L2012 atural history of roionic acidemia Mol

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@ /ore :eam L201# @Y ) lan(ua(e and en


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Sauer S7- O,un J.- SchBab M) et al L2005 4ioener(etics in (lutaryl$coenyme )

dehydro(enase de[ciencyY a role for (lutaryl$coenyme ) J 4iol /hem 2&0Y21&'0

21&'/ross@ef>ubMed

Sauer S7- O,un J.- 6ric,er . et al L200 Intracerebral accumulation of (lutaric and '$

hydro?y(lutaric acids secondary to limited u? across the bloodbrain barrier constitute

a biochemical ris, factor for neurode(eneration in (lutaryl$/o) dehydro(enase

de[ciency J eurochem %!Y&%%%10/ross@ef>ubMed

Sauer S7- O S- Mahrin(er ) et al L2010 .lutaric aciduria tye I and methylmalonic

aciduriaY simulation of cerebral imort and e?ort of accumulatin( neuroto?ic

dicarbo?ylic acids in in ubMed

SchBab M)- Sauer S7- O,un J. et al L200 Secondary mitochondrial dysfunction in

roionic aciduriaY a atho(enic role for endo(enous mitochondrial to?ins 4iochem J

'%&Y10!112/ross@ef>ubMed/entral>ubMed

Smuc,er MD- )llan J- /arterette 4 L200! ) comarison of statistical si(ni[cance tests

for information retrie et al L1%%% Inherited lon($chain '$hydro?yacyl$/o)

dehydro(enase de[ciency and a fetal$maternal interaction cause maternal lierinatol 2'Y100112/ross@ef>ubMed

Strauss *)- 3aoubMed/entral>ubMed
http://dx.doi.org.sci-hub.org/10.1074/jbc.M502845200http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15840571http://dx.doi.org.sci-hub.org/10.1111/j.1471-4159.2006.03813.xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16573641http://dx.doi.org.sci-hub.org/10.1016/j.bbadis.2010.03.003http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20302929http://dx.doi.org.sci-hub.org/10.1042/BJ20060221http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC1525008http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC1525008http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16686602http://dx.doi.org.sci-hub.org/10.1016/S0146-0005(99)80044-5http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10331463http://dx.doi.org.sci-hub.org/10.1093/brain/awm058http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17478444http://dx.doi.org.sci-hub.org/10.1093/brain/awp297http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20032085http://dx.doi.org.sci-hub.org/10.1111/j.1651-2227.2008.00952.xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC2675643http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC2675643http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18647279http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2013.07.008http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4364413http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4364413http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23972786http://dx.doi.org.sci-hub.org/10.1074/jbc.M502845200http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15840571http://dx.doi.org.sci-hub.org/10.1111/j.1471-4159.2006.03813.xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16573641http://dx.doi.org.sci-hub.org/10.1016/j.bbadis.2010.03.003http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20302929http://dx.doi.org.sci-hub.org/10.1042/BJ20060221http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC1525008http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16686602http://dx.doi.org.sci-hub.org/10.1016/S0146-0005(99)80044-5http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10331463http://dx.doi.org.sci-hub.org/10.1093/brain/awm058http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17478444http://dx.doi.org.sci-hub.org/10.1093/brain/awp297http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20032085http://dx.doi.org.sci-hub.org/10.1111/j.1651-2227.2008.00952.xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC2675643http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18647279http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2013.07.008http://www.ncbi.nlm.nih.gov.sci-hub.org/pmc/articles/PMC4364413http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23972786


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Sutton @- /haman *)- .roman )3 et al L2012 /hronic mana(ement and health

suerubMed

:eufel N- 7eit J- 6lechtenmacher / et al L2011 i(h ur(ency lio((i 6- Sada M et al L1%%# /linical outcome of lon($term

mana(ement of atients Bith erinatol 1'Y1'11'#/ross@ef>ubMed

;Bic,ler :- ae(e .- @iderer )- +rster 6- omann .6- 4ur(ard >- *+l,er S L2012

Metabolic decomensation in methylmalonic aciduriaY Bhich biochemical arameters

are discriminatiubMed

Orotocols

@eference 7or,s/ther Sites

Srin(ercom Srin(er>rotocols Srin(erMaterials

6elp 3ontacts
http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2011.08.034http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21963082http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9567-xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23361304http://dx.doi.org.sci-hub.org/10.1016/S0022-3476(05)82005-0http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=7996362http://dx.doi.org.sci-hub.org/10.1002/ajmg.c.30089http://dx.doi.org.sci-hub.org/10.1055/s-2007-994309http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8688100http://dx.doi.org.sci-hub.org/10.1007/s10545-011-9426-1http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22249333http://dx.doi.org.sci-hub.org/10.1007/s10545-013-9621-3http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23797949http://link.springer.com.sci-hub.org/search?facet-content-type=%22Journal%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Book%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22BookSeries%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Protocol%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22ReferenceWork%22http://www.springer.com.sci-hub.org/http://www.springerprotocols.com.sci-hub.org/http://materials.springer.com.sci-hub.org/http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2011.08.034http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21963082http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9567-xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23361304http://dx.doi.org.sci-hub.org/10.1016/S0022-3476(05)82005-0http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=7996362http://dx.doi.org.sci-hub.org/10.1002/ajmg.c.30089http://dx.doi.org.sci-hub.org/10.1055/s-2007-994309http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8688100http://dx.doi.org.sci-hub.org/10.1007/s10545-011-9426-1http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22249333http://dx.doi.org.sci-hub.org/10.1007/s10545-013-9621-3http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23797949http://link.springer.com.sci-hub.org/search?facet-content-type=%22Journal%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Book%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22BookSeries%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Protocol%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22ReferenceWork%22http://www.springer.com.sci-hub.org/http://www.springerprotocols.com.sci-hub.org/http://materials.springer.com.sci-hub.org/


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Nnidade de DoenQas MetabRlicas- Serediatria- osital de S Jo9o- E>E- >orto->ortu(alL%6irst 6aculty of Medicine- /harles Nnira(ue-/ech @eublicL10NO/ >atolo(ia Metabolica- Osedale >ediatrico 4ambino .Fsu- @ome- ItalyL11School of Medicine- Nni


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*lini, fCr *inder$ und Ju(endmediin- Nniaris- 6ranceL'0Nni


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:he re(istry is constructed in a modular Bay- containin( a set of common dataelements for all O)D and N/D as Bell as disease$seci[c folloB$u arameters :here$de[ned al(orithm is summaried in Sul :able 1:he modular desi(n of the re(istry is helful for comaratiSS Statistics 220 Bas used Standard de


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&'da$s (&"da$s

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&'da$s (&"da$s

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atients Bere identi[ed neonatally due to neBborn screenin( LtotalY 1& atients- O)DY1'! atients- N/DY '1 atients or metabolic cascade testin( in hi(h$ris, families Bith are


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iseasegroup

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,n-

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diabetes in O)D re(nancies L55 and that of arterial hyertension in N/Dre(nancies L' ^ Bas similar to that found in re(nancies in (eneral- ie 2$10 ^ for(estational diabetes L.abbe et al 2012 and #! ^ for arterial hyertension L3iu etal 2014 Other medical roblems Bere only reorted in sin(le cases for N/D heaticdisease L)S3 de[ciency- renal disease L)SS de[ciency and O)D renal disease L.)1-sychiatric disease LI)- re$eclamsia L>)- I)- eclamsia L.)1- and eilesy L>)/ardiac roblems Bere not reortede?t- Be studied Bhether there is eostnatal roblems Bere common in O)D Ln ] 111 and N/D Ln ] !2atients- Bith feedin( roblems LO)DY 20 ^- N/DY 1# ^ and hyerbilirubinemia LO)DY% ^- N/DY ! ^ bein( most freKuently reorted Some of these roblems Le( feedin(roblems most li,ely re`ect the be(innin( of a neonatal metabolic crisis- Bhereasothers Le( hyerbilirubinemia are found in the same ran(e as in the (eneraloulation )nthroometrical arameters Bere mostly in the normal ran(e- hoBe


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is

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4old tyes indicate statistically si(ni[cant anthroometric arameters- ie loB birthBei(ht in MM) atients and increased head circumference in .)1 atients

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standard bicarbonate and citrulline than late$onset atients Similarly- symtomaticfemale O:/ carriers Bho had a neonatal metabolic crisis had a hi(her ammonia andtendency toBards hi(her lactate and loBer than those Bith late onset of symtoms)lthou(h early$onset atients Bith />S1- )SS and )S3 de[ciency also seemed to ha


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p6p3/

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Members of the Nrea /ycle Disorders /onsortium- 4atshaB M3- :uchman M- Summar M-

Seminara J L201# ) lon(itudinal study of urea cycle disorders Mol .enet Metab

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4aum(artner M@- +rster 6- Dionisi$ici / et al L201# >roosed (uidelines for the

dia(nosis and mana(ement of methylmalonic and roionic acidemia Orhanet J @are

Dis %Y1'0/ross@ef>ubMed/entral>ubMed

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/handler @J- ;erfas >M- Shans,e S- Sloan J- omann - DiMauro S- enditti /> L200%

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/haman *)- .roman )- Mac3eod E et al L2012 )cute mana(ement of roionic

acidemia Mol .enet Metab 105Y125/ross@ef>ubMed/entral>ubMed

/ole :J L1%%0 :he 3MS method for constructin( normalied (roBth standards Eur J /lin

utr ##Y#50>ubMed

/ole :J- 6reeman J- >reece M) L1%%& 4ritish 1%%0 (roBth reference centiles for

Bei(ht- hei(ht- body mass inde? and head circumference [tted by ma?imum enalied

li,elihood Stat Med 1!Y#0!#2%/ross@ef>ubMed

/ole :J- 7illiams )6- 7ri(ht /M L2011 @eubMed

de *eyer p- alayannooulos - 4enoist J6 et al L200% Multile O>OS de[ciency in

the liediatr @es Y%1%5/ross@ef>ubMed
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http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2011.08.034http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21963082http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9567-xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23361304http://dx.doi.org.sci-hub.org/10.1016/S0022-3476(05)82005-0http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=7996362http://dx.doi.org.sci-hub.org/10.1002/ajmg.c.30089http://dx.doi.org.sci-hub.org/10.1055/s-2007-994309http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8688100http://dx.doi.org.sci-hub.org/10.1007/s10545-011-9426-1http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22249333http://dx.doi.org.sci-hub.org/10.1007/s10545-013-9621-3http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23797949http://link.springer.com.sci-hub.org/search?facet-content-type=%22Journal%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Book%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22BookSeries%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Protocol%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22ReferenceWork%22http://www.springer.com.sci-hub.org/http://www.springerprotocols.com.sci-hub.org/http://materials.springer.com.sci-hub.org/http://dx.doi.org.sci-hub.org/10.1016/j.ymgme.2011.08.034http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21963082http://dx.doi.org.sci-hub.org/10.1007/s10545-012-9567-xhttp://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23361304http://dx.doi.org.sci-hub.org/10.1016/S0022-3476(05)82005-0http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=7996362http://dx.doi.org.sci-hub.org/10.1002/ajmg.c.30089http://dx.doi.org.sci-hub.org/10.1055/s-2007-994309http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8688100http://dx.doi.org.sci-hub.org/10.1007/s10545-011-9426-1http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=22249333http://dx.doi.org.sci-hub.org/10.1007/s10545-013-9621-3http://www.ncbi.nlm.nih.gov.sci-hub.org/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=23797949http://link.springer.com.sci-hub.org/search?facet-content-type=%22Journal%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Book%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22BookSeries%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22Protocol%22http://link.springer.com.sci-hub.org/search?facet-content-type=%22ReferenceWork%22http://www.springer.com.sci-hub.org/http://www.springerprotocols.com.sci-hub.org/http://materials.springer.com.sci-hub.org/


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