Table Of ContentEva Morava
Matthias Baumgartner
Marc Patterson
Shamima Rahman
Johannes Zschocke
Verena Peters Editors
JIMD Repor ts
Volume 33
JIMD Reports
Volume 33
Eva Morava
Editor-in-Chief
Matthias Baumgartner Marc Patterson
(cid:129) (cid:129)
Shamima Rahman Johannes Zschocke
(cid:129)
Editors
Verena Peters
Managing Editor
JIMD Reports
Volume 33
Editor-in-Chief Editor
EvaMorava ShamimaRahman
TulaneUniversityMedicalSchool ClinicalandMolecularGeneticsUnit
NewOrleans UCLInstituteofChildHealth
Louisiana London
USA UK
Editor Editor
MatthiasBaumgartner JohannesZschocke
DivisionofMetabolismandChildren’s DivisionofHumanGenetics
ResearchCentre MedicalUniversityInnsbruck
UniversityChildren’sHospitalZurich Innsbruck
Zurich Austria
Switzerland
ManagingEditor
Editor VerenaPeters
MarcPatterson CenterforChildandAdolescent
DivisionofChildandAdolescent Medicine
Neurology HeidelbergUniversityHospital
MayoClinic Heidelberg
Rochester Germany
Minnesota
USA
ISSN2192-8304 ISSN2192-8312 (electronic)
JIMDReports
ISBN978-3-662-55011-3 ISBN978-3-662-55012-0 (eBook)
DOI10.1007/978-3-662-55012-0
#SSIEMandSpringer-VerlagBerlinHeidelberg2017
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Contents
DifficultiesinDailyLifeandAssociatedFactors,andQoLofChildrenwith
InheritedMetabolicDiseaseandTheirParentsinJapan:ALiteratureReview.... 1
KeikoYamaguchi,RieWakimizu,andMitsuruKubota
SwallowPrognosisandFollow-UpProtocolinInfantileOnsetPompeDisease.... 11
GyaniSwift,MaureenCleary,StephanieGrunewald,SoniaLozano,MartinaRyan,
andJamesDavison
ClinicalandGeneticCharacteristicsofRomanianPatientswith
MucopolysaccharidosisTypeII ......................................... 19
CameliaAlkhzouz,CeciliaLazea,SimonaBucerzan,IoanaNascu,EvaKiss,
CarmencitaLuciaDenes,andPaulaGrigorescu-Sido
GastrointestinalHealthinClassicGalactosemia............................ 27
KellyA.Shaw,JenniferG.Mulle,MichaelP.Epstein,andJudithL.Fridovich-Keil
ManagementofLife-ThreateningTrachealStenosisandTracheomalacia
inPatientswithMucopolysaccharidoses .................................. 33
ChristophKampmann,ChristianeM.Wiethoff,RalfG.Huth,GundulaStaatz,
EugenMengel,MichaelBeck,StefanGehring,TorstenMewes,andTariqAbu-Tair
BrainWhiteMatterIntegrityMediatestheRelationshipBetweenPhenylalanine
ControlandExecutiveAbilitiesinChildrenwithPhenylketonuria............. 41
AnnaHood,JerrelRutlin,JoshuaS.Shimony,DorothyK.Grange,
andDesireeA.White
TheChallengesofaSuccessfulPregnancyinaPatientwithAdultRefsum’s
DiseaseduetoPhytanoyl-CoAHydroxylaseDeficiency ...................... 49
KarolinaM.Stepien,AnthonyS.Wierzbicki,BweeT.Poll-The,HansR.Waterham,
andChristianJ.Hendriksz
NovelHomozygousMissenseMutationinSPG20GeneResultsinTroyer
SyndromeAssociatedwithMitochondrialCytochromecOxidaseDeficiency ..... 55
RonenSpiegel,DevorahSoiferman,AvrahamShaag,StavitShalev,OrlyElpeleg,
andAnnSaada
LethalNeonatalLTBLAssociatedwithBiallelicEARS2Variants:CaseReport
andReviewoftheReportedNeuroradiologicalFeatures ..................... 61
RenataOliveira,EwenW.Sommerville,KyleThompson,JoanaNunes,
AngelaPyle,ManuelaGrazina,PatrickF.Chinnery,Lu´ısaDiogo,
PaulaGarcia,andRobertW.Taylor
v
vi Contents
LeukoencephalopathyduetoComplexIIDeficiencyandBi-AllelicSDHB
Mutations:FurtherCasesandImplicationsforGeneticCounselling............ 69
SabineGrønborg,NiklasDarin,MariaJ.Miranda,BodilDamgaard,
JorgeAsinCayuela,AndersOldfors,GittanKollberg,ThomasV.O.Hansen,
KirstineRavn,FlemmingWibrand,andElsebetØstergaard
PeakJumpPowerReflectstheDegreeofAmbulatoryAbilityinPatientswith
MitochondrialandOtherRareDiseases .................................. 79
ChristopherNewell,BarbaraRamage,AlbertoNettel-Aguirre,IonRobu,
andAnealKhan
RARS2Mutations:IsPontocerebellarHypoplasiaType6aMitochondrial
Encephalopathy? .................................................... 87
TessavanDijk,FredvanRuissen,BregjeJaeger,RichardJ.Rodenburg,
SaskiaTamminga,MerelvanMaarle,FrankBaas,NicoleI.Wolf,
andBweeTienPoll-The
MissedNewbornScreeningCaseofCarnitinePalmitoyltransferase-II
Deficiency .......................................................... 93
AndrewC.Edmondson,JenniferSalant,LynneA.Ierardi-Curto,andCanFicicioglu
Leigh-LikeSyndromeDuetoHomoplasmicm.8993T>GVariantwith
HypocitrullinemiaandUnusualBiochemicalFeaturesSuggestiveofMultiple
CarboxylaseDeficiency(MCD) ......................................... 99
ShantiBalasubramaniam,B.Lewis,D.M.Mock,H.M.Said,M.Tarailo-Graovac,
A.Mattman,C.D.vanKarnebeek,D.R.Thorburn,R.J.Rodenburg,
andJ.Christodoulou
Erratum .......................................................... 109
JIMDReports
DOI10.1007/8904_2016_573
RESEARCH REPORT
Difficulties in Daily Life and Associated Factors, and QoL of
Children with Inherited Metabolic Disease and Their Parents
in Japan: A Literature Review
Keiko Yamaguchi(cid:129)Rie Wakimizu(cid:129)Mitsuru Kubota
Received:18January2016/Revised:18March2016/Accepted:09May2016/Publishedonline:26June2016
#SSIEMandSpringer-VerlagBerlinHeidelberg2016
Abstract To assess the quality of life (QoL) of children in metabolic disorder, such as diet and treatment. The
Japanwithinbornerrorsofmetabolism(IEM)aswellasof psychological health of their caregivers was also poor. To
theirparents,we reviewed 23previousstudies published in improvetheQoLofchildrenwithIEMandoftheirparents,
Japanese and 1 published in English, focusing on the futurecomprehensivequantitativeandqualitativestudiesof
difficulties they encounter in daily life, the factors asso- their QoL and of their subjective support needs are
ciatedwiththesedifficulties,andtheirQoL.Wedividedthe required. Additionally, the specific factors related to the
difficulties and associated factors into three developmental QoL of such individuals need to be explored in large
stages. At the infant stage, individualswithIEMtend to be population-based statistical studies.
at high risk of hypercatabolism. Their parents suffered
anxiety and distress because of the child’s diet therapy and Abbreviations
regarded the parents’ support group as an essential AA Argininosuccinic aciduria
presence, particularly given that IEM is a rare disease. At CD Citrin deficiency
the school-age stage, as their sphere of social relationships GA Glutaric acidemia
expanded, children with IEM became nervous about being HM Hypermethioninemia
comparedwithhealthychildrenoftheirownagebecauseof IA Isovaleric acidemia
their diet therapy. At the adolescence-to-adulthood stage, IEM Inborn error of metabolism
the children suffered medically, economically, and socially. MPS Mucopolysaccharidosis
Even in the absence of any IEM symptoms, the children’s MSUD Maple syrup urine disease
QoL was affected by the demands associated with the OA Organic acidemia
PA Propionic acidemia
PKU Phenylketonuria
Communicatedby:GeorgHoffmann
K.Yamaguchi(*)
DepartmentofNursingScienceMaster’sProgram,GraduateSchoolof
ComprehensiveHumanSciences,UniversityofTsukuba,
1-1-1Tennodai,Tsukuba,Ibaraki305-8575,Japan
Introduction
e-mail:[email protected]
R.Wakimizu
According to the Japanese Ministry of Health Labour and
FacultyofMedicine,DivisionofHealthInnovationandNursing,
DepartmentofChildHealthCareNursing,UniversityofTsukuba, Welfare(2013),thenumberofpatientsinJapanwithinborn
1-1-1Tennodai,Tsukuba,Ibaraki305-8575,Japan errorsofmetabolism(IEM)wasabout19,000in2013.The
e-mail:[email protected]
Ministry has been supporting several studies on the
M.Kubota diagnosis and treatment of IEM (The Japanese Ministry of
DepartmentofGeneralPediatricsandInterdisciplinaryMedicine,
Health Labour and Welfare 2015). As a result of the
NationalCenterforChildHealthandDevelopment,2-10-1Okura,
expansion of the newborn tandem mass screening test,
Setagaya-ku,Tokyo157-8535,Japan
e-mail:[email protected] studies not only on diagnosis and treatment but also on the
2 JIMDReports
psychological and social aspects of the parents have been Data Analysis
conducted (Sakoda et al. 2011; Abe 2012). At the same
time, researchers have highlighted the importance of how We intensively read the 24 articles and focused on the
patients with IEM and their families should be supported results related to difficulties faced by children with IEM
after diagnosis (Matsubara 2010). andbytheirparentsindailylife,thefactorsassociatedwith
Most patients with IEM have to follow a strict diet those difficulties, and their QoL. We classified the results
therapythroughouttheirlifeandtolivewiththepermanent according to the child’s developmental stages: infant stage,
risk of metabolic crises (Zeltner et al. 2014). The diet school-age stage, and adolescence-to-adulthood stage. And
therapy may affect many aspects of their daily life and wesummarizedwhathasalreadybeeninvestigatedinterms
quality of life (QoL), as well as of their family members’. oftheirQoL.Finally,weconsideredfutureissues thatneed
In countries other than Japan, some studies have been to be addressed to improve the QoL of these children and
conducted on the daily life and QoL of patients with IEM their parents.
andoftheirparents(LambertandBoneh2004;Simonetal.
2008;Stockler etal.2012;Cazzoria etal.2014).Asoneof
thefactorsassociated with their QoL,childrenwith IEMin Results
Turkey with bad diet compliance reportedly had lower
scores in two aspects of QoL assessment: school labeling Table 1 shows the reviewed articles, and Fig. 1, the
andperceptionofdisease(Eminogluetal.2013).However, difficultiesreportedthereinasexperiencedbychildrenwith
only a few studies in Japan have been conducted and these IEM and their parents with regard to daily life, as well as
focused mainly on the patients’ and on their mothers’ QoL the associated factors at each stage of the child’s life. We
(Kubo et al. 2008; Okano et al. 2013). have added the medical and clinical aspects of IEM to
In this study, we sought to understand the problems provide a more complete picture of their life. Other than
encounteredinthedailylivesofJapanesechildrenwithIEM thoseonMPS,mostofthestudiesincludedonlyverysmall
and of their parents by reviewing what has already been numbers of families, with many including only one family.
investigatedintermsoftheirdifficultiesindailylifeandthe
factorsassociatedwiththosedifficulties,andintermsoftheir Difficulties in Daily Life and Associated Factors
QoL.Andweconsideredfutureissuesthatneedtobetackled
toimprovetheQoLofthesepatientsandtheirfamilies. Infant Stage
Newborn Mass Screening, Specialized Examinations, and
Methods DiagnosisInJapan,newbornswhotestpositiveforIEMon
newborn tandem mass screening have to undergo several
Data Sources and Search Strategies specialized examinations such as amino acid analysis, gas
chromatography and mass spectroscopy (GC/MS), enzyme
To identify eligible articles for this literature review, we assay, and gene analysis. Doctors specializing in IEM then
conductedasearchofthePubMeddatabaseandofthemost make a diagnosis (Endo et al. 2013).
popular database in the medical discipline in Japan – the Infants at High Risk of Hypercatabolism and Parents’
Japan Medical Abstracts Society (version 5). The search Difficulty in Preventing the Child’s Hypercatabolism
was conducted using Japanese and English keywords such Generally speaking, infants easily contract infections;
as “inborn error of metabolism,” the names of particular thus, they are at high risk of hypercatabolism. In one case
types of IEM, and “daily life” or “QoL.” At the initial of maple syrup urine disease (MSUD), the child was
searchinMarch2015,weretrieved6,692publicationsfrom admitted to hospital 30 times before the age of 10 years
thetwodatabases. After readingthetitles andabstracts,we because of hypercatabolism caused by infections
excluded those articles focusing only on the diagnosis or accompanied by diarrhea and fever (Fujiwara 2013). It is
the medical treatment or that were not about Japanese difficulttopreventinfantswithIEMfrombecomingsickin
patients. After that, we conducted an additional search daily life. One mother of a child with propionic acidemia
using quotations within quotations to ensure the compre- (PA)couldnotrecognizethesignsofsevereacidosisinher
hensiveness of the review. So as notto omit any reports on childbecauseshethoughtthechildwasjusthavinganother
IEMstudiesinJapan,weincludednotonlyoriginalarticles cold (Taketa et al. 1991). Families are also concerned
but also feature articles and proceedings. Finally, we about the risk of sickness for their child (Fujiwara 2013)
targeted 24 publications from 1987 to 2014. Only one of because IEM causes, among others, hypercatabolism,
thearticleswaswritteninEnglish,andtherestwerewritten psychomotor retardation, and intellectual disability
in Japanese. (Yuhara et al. 1991).
JIMDReports 3
Table1 Listof24eligiblearticles
Metabolic Life Summaryofarticlesfocusedondifficultiesindailylifeand
Author(s) Articletype disease N stagea associatedfactors,andQoL
Abe(2012) Proceedings PKU 1b 1 Importanceofcooperationwithfamiliesincaringforchildren
Fujiwara Featurearticle PKU,MSUD 5b 1,2,3 Difficultyinpreventionofhypercatabolismcausedbychild’s
(2013) sickness,sharingtheiranxietyanddistressrelatedtoraising
childrenwithIEM,andhavingpeoplearoundthem
understandtheirchild'sdiettherapy;importanceofaparents’
supportgroupandgeneticcounselingtocopewithanxiety
anddistress,worriesaboutnextpregnancy,andfinancial
difficultiesfromadulthoodrelatedtodiettherapy
Ishiyama Originalarticle PKU 4b 1,2 Difficultyofmanagementofdiettherapywithdevelopmental
etal.(1987) stages;psychologicalburdenofchild'sdiagnosisanddiet
therapy
Kashiwagi Proceedings OA N/A 1,2,3 Parents’anxietyanddistressrelatedtohome-rearingof
(2011) childrenwithIEM;lackofinformationondiseaseand
treatment;socialdiscriminationsuchasrefusalofpermission
toenternurseryschool
Kashiwagi Proceedings IMD N/A 1,2,3 Difficultyassociatedwithsharingtheiranxietyanddistress
(2012) aboutraisingachildwithIEM;difficultieswithdiettherapy;
financialdifficultiesfromadulthoodrelatedtodiettherapy
Katoand Originalarticle MMA,PA, 19c N/A Sufferingfromsocialdiscriminationwhentakingoutinsurance
Kashiwagi GA,IA,AA,
(2010)
Komatsu Originalarticle N/A 16c N/A Sufferingfromsocialdiscriminationwhentakingoutinsurance
etal.(2011)
Kubo(2007) Originalarticle MPS 4b 1,2 Positiveimpactofschoolasachancetoacquirethe
fundamentalhabitofdailylifeandtoreducemothers’stress
andfatigue
Kubo(2010) Originalarticle MPS 94(4)b N/A LackofinformationonMPS;guiltfeelingsassociatedwiththe
child'sdisease
Kuboand Originalarticle MPS 11b 1,2 LackofinformationonMPSorchild’scare;necessityofa
Tamura parents’supportgroupforgatheringinformationaboutMPS
(2007)
Kuboetal. Originalarticle MPS 94(10)b 1 Delayeddiagnosiscausedbymedicalprofessionals’lackof
(2008) knowledgeofMPS
Kuboand Originalarticle MPS 94b N/A GeneralHealthQuestionnaire30:QoLof28-to70-year-old
Tazaki caregiversofchildrenwithMPS;themeanQoLscorewas
(2008a) higherthanthatforhealthyparents,indicatingpoor
psychologicalhealth;theassociatedfactorofQoLwas
bathingassistance(b¼0.363,r¼0.049)
Kuboand Originalarticle MPS 94b N/A GeneralHealthQuestionnaire30:QoLof28-to71-year-old
Tazaki caregiversofchildrenwithMPS;thesignificantfactorsof
(2008b) QoLwerebathingassistance(r¼0.465)andimpossibility
ofcommunicationwiththeirchildren(r¼0.38)
Manbaetal. Originalarticle PKU,HM, 11b 1,2 Mosthelpfulroleofparents’supportgroupforfamiliesinthe
(1997) MSUD,AA earlyphaseafterchild'sdiagnosis;parents’supportgroupas
aninventoryoftheirexperienceforfamiliesraisingchildren
foralongtime;problemsrelatedtothechild'sexpanding
sociallife;sufferingfromsocialprejudicebecauseofgenetic
disease
Matsumoto Proceedings PKU 1b 1 Fulfillmentfromraisingachild;expectationofachild's
etal.(2014) development
Nakataetal. Originalarticle PA 1b 1 Difficultyofdiettherapybecausethechildcouldnottake
(1998) enoughmilk
Nikaidouand Featurearticle IEM N/A 1 Psychologicalburdenassociatedwiththechild’slifeand
Kosuga prognosis
(2014)
(continued)
4 JIMDReports
Table1 (continued)
Metabolic Life Summaryofarticlesfocusedondifficultiesindailylifeand
Author(s) Articletype disease N stagea associatedfactors,andQoL
Okano(2011) Featurearticle PKU N/A 1,2,3 Difficultyofmanagementoftheamountofmilkandblood
levelsofphenylalanine;necessityofeducationaboutdiet
therapyfromchildhood;necessityofcontrolduring
pregnancyofpatientswithPKU
Okanoetal. Originalarticle CD 52b 1,2,3 PedsQLMultidimensionalFatigueScale,PedsQLGeneric
(2013) CoreScale:QoLofchildrenwithCDaged1–22yearsbased
onself-reportsandproxyreportsbytheirguardians;themean
scoresofbothwerelowerthanthoseforhealthychildren
Shigematsu Originalarticle PA 1b 1 Difficultyofdiettherapybecausethechildcouldnottake
etal.(2000) enoughmilk;responsibilityofthechild'sdiettherapy
concentratedonthemother;sufferingfromsocial
discriminationfromgrandparents’generation
Taketaetal. Featurearticle PA 1b 1 Difficultyinpreventingchild’ssickness;importanceof
(1991) educationatdischargefromhospitalforthefirsttime
Uenoetal. Featurearticle IA 2b 1 Strugglesofcopingwithproblemsrelatedtochild’sfood
(1990) restriction
Yoshinoetal. Featurearticle PKU N/A 3 Financialdifficultyfromadulthoodassociatedwithtreatment
(2010)
Yuharaetal. Featurearticle PKU N/A 1,2,3 Realizationandcomparisonwithhealthchildrenaboutdiet;
(1991) temptationtoeattherestrictedfood;importanceofspecial
controlofpregnancy
aChild’slifestage:1.infantstage2.school-agestage3.adolescence-to-adulthoodtransitionalstage
bN:numberoffamilies
cN:numberofinsurancecompanies
Child’s Adolescence-to
Infant stage School-age stage
life stage -adulthood stage
Financial difficulty
Struggling with diet therapy
High risk of hypercatabolism due to no aid for
as their social life expands
diet therapy
Diagnosed
child Social discrimina(cid:3)on
Essen(cid:3)al presence of the parents’ support group
Parents Difficulty in preven(cid:3)ng the Difficulty with diet therapy as their child’s Social discrimina(cid:3)on
child’s hypercatabolism social life expands
Difficulty and responsibility of child’s
Worries about the next pregnancy
diagnosis and diet therapy
Newborn screening Strict metabolic control
during pregnancy
Medical Specialized examina(cid:3)on
involvement Diagnosis Maintaining diet therapy
Regular clinic visits
Difficul(cid:3)es in daily life Associated factors Medical involvement
Fig.1 Difficultiesindailylifeandassociatedfactors,andmedicalinvolvementateachlifestageofdiagnosedchildren
