Duchenne Muscular Dystrophy With Low Acidic α-Glucosidase Activity Two Case Reports and Literature Review 2022 Xiufang He.pdf

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CASEREPORT
published:01June2022
doi:.855510
DuchenneMuscularDystrophyWith
LowAcidicα-GlucosidaseActivity:
TwoCaseReportsandLiterature
Review
XiufangHe1,2†,XuandiLi1,2†,YueseLin1,2,HongjunBa1,2,HuiminPeng1,2,LiliZhang1,2,
LingZhu1,2,YouzhenQin1,2*andShujuanLi1,2*
1DepartmentofPediatricCardiology,HeartCenter,TheFirstAffiliatedHospital,SunYat-senUniversity,Guangzhou,China,
2KeyLaboratoryonAssistedCirculation,MinistryofHealth,Guangzhou,China
Editedby:
,
NemoursChildren’sHealth,Background:Pompediseaseisusuallyconsideredinchildrenwithelevatedcreatine
UnitedStateskinase(CK)levelsanddecreasedacidicα-glucosidase(GAA),
Reviewedby:thereareexceptions,suchasGAApseudodeficiencyalleles,whichresultinlowerGAA
MigvisMonduy,,wereporttwocasespresenting
NemoursChildren’sHospital,
UnitedStateswithhighCKlevelsandlowGAAactivitywhowereultimatelydiagnosedwithDuchenne
TingliangLiu,musculardystrophy(DMD).
ShanghaiChildren’sMedicalCenter,
ChinaCasePresentation:Case1patientwasa2-month-oldboywhopresentedwith
*Correspondence:anextremelyhighserumCKlevel(5,480∼11,880U/L)andlowGAAactivity
YouzhenQin().Thewhole-exomesequencingdidnotfindthepathogenicGAA
******@
ShujuanLigenemutation,however,therewasaDMDgenehemizygousvariation(>T,
******@)inheritedfromhismother,whichwasverifiedbythefirst-generation
†

equallytothisworkandsharefirst
authorshipdeficiencyalleles(>A,>A,),which
werebelievedtoinducethepatient’,theboywasdiagnosed
Specialtysection:withDMD,-
Thisarticlewassubmittedto
GeneticsofCommonandRaremonth-oldboypresentingwithasignificantincreaseinCKlevel(12,408∼24,828U/L).
Diseases,HisbloodGAAactivity(colorimetricmethod),hiswhole-
asectionofthejournal
FrontiersinPediatricsexomesequencingdidnotfindthepathogenicmutationoftheGAAgene,butaDMD
Received:15January2022genehemizygousvariation(,),hencehewasdiagnosed
Accepted:,thecase2patientwasnotaslowasthecase
Published:01June20221patient,mainlybecausehistwoGAApseudodeficiencyalleleswereheterozygous.
Citation:
HeX,LiX,LinY,BaH,PengH,Conclusion:
ZhangL,ZhuL,QinYandLiS(2022)shouldbeawarethatpseudodeficiencyallelescancauselowGAAactivitiesbutnot
DuchenneMuscularDystrophyWith
LowAcidicα-GlucosidaseActivity:
TwoCaseReportsandLiteraturedeficiencyallelesfrompatientswithsomemusculardisorderdiseasessuchasDMD.
:855510.
doi:.855510Keywords:acidα-glucosidase,pseudodeficiencyalleles,Duchennemusculardystrophy,creatinekinase,child
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INTRODUCTION11asa2-month-
highCKlevelsof5,480∼11,880U/Lwithlesserelevationsof
NeuromusculardiseasessuchasDuchennemusculardystrophyalaninetransaminase(ALT197U/L),aspartatetransaminase
(DMD)andsomeglycogenstoragediseaseslikePompe(AST455U/L),andlacticdehydrogenase(LDH788U/L).Due
diseaseareconsideredinchildrenhavinghighbloodcreatinetothehighCKlevel,GAAactivitywastestedandfoundan
kinase(CK)(colorimetricmethod,
TheDMDisanX-linkedrecessivegeneticdiseasecausedbyreferencevalueof>14nmol/1h/mg).Urineorganicacids,dry
,andacylcarnitineanalysis
importanttomaintainthemusclefiber’
,theboydid
(DNAnothaveeithersuckingorswallowingdifficulties,poormuscle
testing)andamusclebiopsytestconfirmthediagnosisinmosttone,orswellingtongueasthoseofearly-
cases(1).1weeklater,whole-exomesequencingwascarriedoutand
Pompedisease,alsocalledGlycogenstoragediseasetypetheresultshowedthathedidnothavepathogenicmutations
II,isanautosomalrecessivemetabolicdisordercausedbyanoftheGAAgenebutaDMDgenehemizygousvariation(c.
accumulationofglycogeninthelysosomeduetodeficiencyofthe7657C>T,)-generation
lysosomalacidalpha-glucosidase(GAA)enzyme,whichiscausedsequencingverifiedhishemizygousvariationwasinheritedfrom
-upofglycogencauseshismotherwhohadaheterozygousvariation(Figure1Aand
progressivemuscleweakness,particularlyintheskeletalmusclesSupplementaryDataSheet).Concurrently,wefoundthathehad
(>A,
theearly->A,).Thesefindings
inthelate-
madebyestimatingtheGAAactivityandgenetictesting(2).,wecheckedtheCK
However,duetothepseudodeficiencyalleles,theGAAactivitylevelsforhisfamilyandfoundthathismother(37yearsold)and
levelsmightbefalsepositive(3).hissister(8yearsold)hadasymptomaticelevatedCK,whichwere
TheprevalenceofPompediseaseisabout2in100,,069U/L,,theGAAactivity
theotherhand,theprevalenceofDMDinmalesisabout10intestingwasperformedforthefamilyaswell,andtheresultswere
100,,
theclinicalfeatures,,activity,andtheirGAAgenetictestingshowedpseudodeficiency
cliniciansneedtobecarefulindifferentialdiagnosis,especiallyallelesaswell.

forPompediseaseisenzymereplacementtherapy,whileitneedsCase2
multidisciplinarymanagementinDMDwithoutafavorablecureAboy,bornat39weeksofgestationalageandweighed
(2,4).Sincethetreatmentandprognosisofthetwodiseases3,200g,washospitalizedbecauseofneonatalpneumonia
aredifferent,wehighlighttheaccuratediagnosisanddifferentialandfoundsignificantlyincreasedCK,rangingfrom3,400
diagnosis,,995U/,hewasadmittedtoour
Inthisarticle,wereporttwoinfantswithhighCKlevelshospitaltore-

,theirgenetictestingidentifiedDMDmuscletoneandmotordevelopmentwerenormalforhisage,
genemutationandGAApseudodeficiencyalleles,
,408∼24,828U/L,ALTof168U/L,
emphasizethatwhenfacingapatientwithincreasedCKandASTof253U/L,andLDHof973U/
decreasedGAAactivity,(referencevalueof
pseudodeficiencyallelesandconsiderthediagnosiscautiously.>14nmol/1h/mg).Urineorganicacids,dryfilterpaperblood
spotaminoacid,andacylcarnitineanalysisshowednegative
,thepatientwassupposed
,hisGAAactivitywasnot
extremelylow,soweperformedthewhole-exomesequencing
Case11weeklater,whichfoundthathehadaDMDgenehemizygous
A2-month-oldbabyboy,whowasbornat38weeksofgestationalmutation(:,)and
ageandweighed3,800g,hadabloodtestbecauseofjaundicetwoGAAheterozygouspseudodeficiencyalleles(>A,
>A,),buthadno
-generationsequencingverified
distress,muscleweakness,feedingdifficulties,failuretothrive,hisDMDgenehemizygousvariationwhichwasinheritedfrom
(Figure1Band
(AIMS)SupplementaryDataSheet).ThetwoGAAheterozygouspseudo
showedhismotordevelopmentasnormal,,
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FIGURE1|DuchennemusculardystrophyDMDgenesequencingforthepatientsandtheirlinealrelatives.(A)ResultofDMDgenesequencingincase1.(B)Result
ofDMDgenesequencingincase2.
TABLE1|Comparisonofacidicα-glucosidase(GAA)activityandGAAvariantsbetweenprobandsandtheirfamily.
GAAactivity(colorimetricmethod)nmol/1h/mgGAAvariantsHomozygoteorheterozygote
>AHomozygote
>AHomozygote
>AHeterozygote
>AHeterozygote
>AHeterozygote
>AHeterozygote
>AHomozygote
>AHomozygote
>AHeterozygote
>AHeterozygote
>AHeterozygote
>AHeterozygote
>AWildtype
>AWildtype
,sothefamilieswereanxiousaccordingly
GAAactivitiesofhisfamilyandfoundthathismother(27yearsaboutthedelayedmotorability,incapacityontakingcareof
old)hadahighCKlevelof221U/LandlowGAAactivityofthemselves,
(Table1).primarilyaffectedskeletalmuscles,itultimatelyledtosystemic
muscleweakness.
PerceptionoftheFamiliesIntermsoftheriskofoffspring,Pompediseasewasan
AtthetimewhenthebabieswerefoundCKelevated,theyautosomalrecessivedisorder,whileDMDwasX-linkrecessive
,,

Pompediseasecouldbeclassifiedasearly-onsetandlate-,

worriedabouttheonsettime,especiallytheinfantiletype,whichexaminationduringthebirthofthefutureoffspring.
woulddamagethemyocardium,andleadtoheartfailureorIntermsoftreatmentmanagement,bothdiseasesaffected
-systemthatrequiredmultidisciplinaryintegrated
Weekslater,,Pompediseasewastreatablewith
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enzymereplacementtherapy,butitwastooexpensiveforthempseudodeficiencyalleles,>A()and
,>A(),theonewhoseGAAactivitywas
,

disease,prolongthesurvivaltime,
AcorrectdiagnosiscouldsavethemfromwastingvaluabletimepopulationorpatientswithPompediseasecouldhaveGAA

Finally,thefamiliesfullyunderstoodthetransitiondeficiencyallelesinahealthypopulationandpatientswith
fromtheinitialdiagnosisofPompediseasetothedefinitePompediseasearesimilar,buthomozygouspseudodeficiency