Braz. j. . vol.82 número3

BrazJOtorhinolaryngol.2016;82(3):281---284

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Audiologic

evaluations

of

children

with

mucopolysaccharidosis

夽

C

¸a˘

gıl

Gökdo˘

gan

,

¸enay

S

Altinyay

,

Ozan

Gökdo˘

gan

,

Hakan

Tutar

,

Bülent

Gündüz

_{, ˙Ilyas}

_Okur

_,

_Leyla

_Tümer

_,

_Yusuf

_Kemal

_Kemalo˘

_glu

a_{DepartmentofAudiology,GaziUniversityHospital,Ankara,Turkey} b_{DepartmentofENT-HNS,MemorialHospital,Ankara,Turkey} c_{DepartmentofENT-HNS,GaziUniversityHospital,Ankara,Turkey}

d_{DepartmentofPediatricNutritionandMetabolism,GaziUniversityHospital,Ankara,Turkey} e_{DepartmentofPediatricEndocrinology,GaziUniversityHospital,Ankara,Turkey}

Received16December2014;accepted5May2015 Availableonline25September2015

KEYWORDS

Mucopolysaccharido-sis;

Hearingloss;

Audiologicevaluation

Abstract

Introduction:Mucopolysaccharidosisisahereditarylysosomalstoragedisease,whichdevelops duetoadeficiencyintheenzymesthatplayaroleinthemetabolismofglycosaminoglycans (GAG).Theincidenceofmucopolysaccharidosisis1/25,000,withautosomalrecessive inheri-tance(exceptforMPSII).Mucopolysaccharidosisoccursinsevendifferenttypes,eachwitha differentcongenitaldeficiencyoflysosomalenzymes.Inmucopolysaccharidosispatients,even thoughprogressionofclinicalfindingsisnotprominent,thediseaseadvancesandcausesdeath atearlyages.Facialdysmorphism,growthretardation,mentalretardation,andskeletalorjoint dysplasiaarethemostfrequentlyfoundsymptomsinthesepatients.

Objective: Thepurposeofourstudyistopresentthetypesofhearinglosstypesand tympano-metricfindingsofpatientswithmucopolysaccharidosisreferredtoourclinicwithsuspicionof hearingloss.

Methods:After otorhinolaryngological examination, 9 patients with different types of mucopolysaccharidosis, underwent to immittance and audiometric evaluations, performed accordingtotheirphysicalandmentalabilities,andages,inordertodeterminetheirhearing thresholds.

Results:Theaudiometricfindingsofthe9patientsfollowedwithmucopolysaccharidosiswere reportedseparatelyforeachcase.

夽 _{Pleasecitethisarticleas:Gökdo˘ganC¸,AltinyayS¸,Gökdo˘ganO,TutarH,GündüzB,Okur ˙I,etal.Audiologicevaluationsofchildrenwith}

mucopolysaccharidosis.BrazJOtorhinolaryngol.2016;82:281---4. ∗_{Correspondingauthor.}

E-mail:[email protected](C¸.Gökdo˘gan).

http://dx.doi.org/10.1016/j.bjorl.2015.05.007

1808-8694/©2015Associac¸˜aoBrasileirade OtorrinolaringologiaeCirurgiaC´ervico-Facial.Published byElsevierEditoraLtda.Allrights

282 Gökdo˘ganC¸etal.

Conclusion:Based onthehigh frequencyofhearing lossin mucopolysaccharidosispatients, earlyanddetailed audiologicalevaluationsarehighlydesirable.Therefore,regularand sys-tematicmultidisciplinaryevaluationsareveryimportant.

© 2015Associac¸˜ao Brasileira de Otorrinolaringologiae CirurgiaC´ervico-Facial. Publishedby ElsevierEditoraLtda.Allrightsreserved.

PALAVRAS-CHAVE

Mucopolissacaridose; Perdaauditiva; Avaliac¸ãoaudiológica

Avaliac¸ãoaudiológicaemcrianc¸ascommucopolissacaridose

Resumo

Introduc¸ão:Mucopolissacaridose (MPS) é uma doenc¸a hereditária de depósito lisossômico, decorrentedadeficiênciadasenzimasqueinfluenciamometabolismodosglicosaminoglicanos (GAGs).A incidênciade MPS é de1/25.000 habitantes, resultante deheranc¸a autossômica recessiva(excetonocasodeMPSII).MPS seapresentanaformadesetetiposdiferentese, emcadatipo,ocorreumadeficiênciacongênitadistintadeenzimaslisossômicas.Emboraem pacientescomMPSosachadosclínicosnãosejamgeralmenteobservados,adoenc¸aprogrideem seucursonaturalecostumalevaraóbitopacientesmuitojovens.Dismorfismofacial,retardo decrescimento,retardo mentaledisplasiaesquelética ouarticularsãoossinaisesintomas maisfrequentementeobservadosnessespacientes.

Objetivo:Afinalidadedopresenteestudofoiapresentarostiposdeperdaauditivaeosachados timpanométricosdepacientescomMPSencaminhadosparanossaclínicacomsuspeitadeperda auditiva.

Método: Emseguidaaoexameotorrinolaringológico,novepacientescomdiferentestiposde MPS,foramsubmetidosaavaliac¸õesimitanciométricasetestesaudiométricosdeacordocom suafaixaetáriaeficiênciafísicaemental,nointuitodeidentificarseuslimiaresauditivos.

Resultados: Os achados audiométricos dos nove pacientes acompanhados por MPS foram descritosseparadamenteparacadacaso.

Conclusão:Baseado naaltafrequência deperdaauditivaem pacientescomMPS, avaliac¸ão audiológicaprecoceedetalhadaéaltamentedesejável.Paratanto,éimportantequesejam realizadosavaliac¸õesmultidisciplinaresperiódicasesistemáticas.

©2015Associac¸˜aoBrasileira deOtorrinolaringologiaeCirurgiaC´ervico-Facial.Publicadopor ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Mucopolysaccharidosis(MPS)isahereditarylysosomal stor-age disease, which develops due to the deficiency in the enzymes that play a role in the metabolism of glycosaminoglycans (GAG). Progressive GAG accumulation causesadvancedgrowthretardation, skeletaldeformities, hearingloss,weakjointmovement,andfacialdysmorphism. Inaccordancewiththedeficiencyoftheknown11enzymes, MPS has seven sub-types (MPS I, MPS II, MPS III, MPS IV, MPSVI,MPSVII,MPSIX).AlthoughtheincidenceofMPSin accordancewithitssub-typesvaries,ageneralincidenceof 1/25,000hasbeenreported.1---3

InpatientswithMPS,hearinglossisobserveddueto var-ious reasons. Conductive hearing loss (CHL) may develop due to recurrent upper respiratory tract infections and serousotitismediaorbonechaindeformities.Sensorineural hearingloss(SHL)isthoughttobecausedduetothe accu-mulationofGAGinthecochlea,auditorynerve,andbrain stem.Inmanypatients,mixed-typehearingloss,alongwith thesymptomsofconductiveandsensorineuralhearingloss, canalsobeseen.InCHLrelatedtomiddleeareffusion,while theventilation tubeimplementation isfrequently usedas

treatment, hearing aidsareadvised in SHL.4---7 _Early diag-nosisofhearinglossescarriesgreatimportanceintermsof early intervention in MPSpatients, aswell asin allother patients.8,9

The purpose of the present study was to present the hearing loss type, degree, and tympanometric findings of patientswithMPS,whoaredirectedtothisclinicwiththe suspicionofhearingloss.

Methods

Audiologicevaluationsofchildrenwithmucopolysaccharidosis 283

Table1 Degreeofhearingloss(dBHL).

Degreeofhearingloss Hearinglossrange(dBHL) Normal −10to15

Slight 16---25 Mild 26---40 Moderate 41---55 Moderatelysevere 56---70 Severe 71---90 Profound 90+

Table2 Tympanogramtypes(daPa).

Tympanogramtype Pressureintervals(daPa) TypeA +50to(−150)

TypeB −400

TypeC −150to(−399)

testswhichareappropriateforthepatients’ages,physical andmentalefficiencies,andboth airandboneconduction thresholdsweredeterminedat250,500,1000,2000,4000, 6000,and8000Hz.

The hearing loss levelswere determinedby taking the averageofpuretoneairconductionthresholds,determined at0.5,1,2,and4kHz,inaccordancewiththeintervalsgiven inTable1.

Hearlosswasclassifiedunderthreegroupsasconductive, mixed,andsensorineural.ForCHL,whilethebonehearing thresholdswerepresentaudiometrically(lessthan20dB),it hasbeenacceptedthat;theaverageair-bonegapin0.5,1, 2kHztobemorethan15dB;inmixedtypehearinglosses, bonehearingthresholdstobe20dBandoveraudiometrically andtheaverageair-bonegaptobemorethan15dBin0.5, 1,2kHz;insensorineuralhearingloss(SHL),thedifference betweentheairandboneconductionthresholdstobeless than15dBinaveragein0.5,1,2kHz.

In the tympanometrical evaluation, 225Hz probe tone signalswereused.Thetympanogramtypeswereevaluated inaccordancewiththevaluesgiveninTable2.

Statisticalanalysis

For the statistical analysis, SPSS version 16.0 (SPSS Inc., Chicago, IL, United States) was used. For the age aver-ageandstandarddeviation(SD),descriptivestatisticswere developed.

Results

TheageaverageofthetotalofninepatientswithMPS,four female (44.44%) and five male (55.55%), was determined as5.66±2.73.TherewerethreecasesofMPSVI(33.33%), threecasesofMPSI(33.33%),onecaseofMPSIII(11.11%), andtwocasesofMPSIV(22.22%)thatwerediagnosed.Cases MÖand EÖ aresiblings; ˙IK and ˙IK 2 are twins.The other fivepatientsarenotrelated.Thedegreeofhearingloss,its type,andtympanometricalfindings areshown in Table3. Thereweresixears withconductive hearingloss(33.33%) (HLoneear:slight;HLoneear:mild;HLtwoears:moderate, andHLtwoears:moderatelysevere); 12ears withmixed hearingloss(66.66%)(HLtwoears:mild;HLfourears: mod-erate,HLfiveears:severe,andHLoneear:profound)were determined.Therewere14earswithTypeBtympanogram (77.77%),threeearswithTypeCtympanogram(16.66%),and oneearwithTypeAtympanogram(5.55%).E.C¸.,B.E.B.,and MSEhadabilateralventilationtube(VT)inserted.Although theotherpatientswereadvised regardingtheVT applica-tionaswell, ithasnotbeen carriedoutupon thewishof theirfamilies.WiththeexceptionofMÖandBEB,although allpatientswereadvisedtousehearingaids,thefamilies didnot adoptthe useof these devicesand didnot come regularlyforfollow-ups.

Discussion

In cases with MPS (Table 4), the initiation of treatment in early stages carries great importance in terms of the prognosisofthedisease.However,duetothelate appear-ance of the symptoms, the definite diagnosis range is 3---4 years of age. In the follow-up of the stages of the treatmentsofpatients withMPS, theotolaryngologistand audiologists have a significant role in multidisciplinary teamwork.Recurrent serous otitismedia and hearingloss

Table3 AudiometricalfindingsofpatientswithMPS.

Patient Agea _{Diagnosis Tympanometricalfindings Typeofhearingloss Degreeofhearingloss}

Right Left Right Left Right Left

MÖ 9 MPSVI TypeC TypeA Conductive Conductive Slight Mild

EÖ 4 MPSVI TypeC TypeC Mixed Mixed Moderate Moderate

˙IK 3 MPSI TypeB TypeB Mixed Mixed Severe Severe

˙IK2 3 MPSI TypeB TypeB Mixed Mixed Severe Severe

EC¸ 9 MPSVI TypeB TypeB Conductive Conductive Moderate Moderatelysevere

SD 8 MPSIV TypeB TypeB Mixed Mixed Moderate Mild

BEB 6 MPSI TypeB TypeB Conductive Conductive Moderate Moderatelysevere

MSE 7 MPSIV TypeB TypeB Mixed Mixed Moderate Moderate

YCE 2 MPSIII TypeB TypeB Mixed Mixed Severe Profound

284 Gökdo˘ganC¸etal.

Table4 Air and boneconduction thresholdsof patients withMPS(dBHL).

Patient Averageair conduction thresholds (500---4000Hz)

Averagebone conduction thresholds (500---4000Hz) Right Left Right Left MÖ 22.5 26.25 6.25 6.25 EÖ 65 57.5 30 30 ˙IK 70a ₃₅b

˙IK2 70a ₄₅b

EC¸ 46.25 60 12.5 12.5

SD 47.5 38.75 18.75 22.5

BEB 51.25 56.25 15 15

MSE 43.75 45 18.75 18.75

YCE 81.25 90 22.5 22.5

a_{Theairconductionthresholdshavebeendeterminedinfree}

field.

b _{The bone conductionthresholds have been determinedin}

accordancewiththespeechrecognitionthresholds.

that develops in individuals within this disease group are the reasons why better, long-term follow-ups should be done.Hearinglosscanbeseeninvarioustypesanddegrees in MPS in general.10---13 _{Overall, conductive hearing losses} due to chronic effusion and eustachian tube dysfunction areseenmore inpatients withMPS; the incidenceofSHL hasnotbeendeterminedveryclearly.10

Although conductiveand mixed-type hearing losswere observedinthecasesofthepresentstudy,SHLcompatible withliteraturehasnotbeendetermined.Inthestudies con-ducted,it wasstatedthattheincidenceof mixedhearing lossis more,andthat thisfactis relatedwithage.While conductivehearingloss isdeterminedinearlyagesandin patientswhoarediagnosedearlier,ithasbeenstatedthat mixedhearingloss can be observed,and that thisrate is between33%and71%asageincreases.Inthepresentcases, degreeofhearinglosswasdeterminedfromslighttosevere. This difference is considered to be due to GAG’s exces-sive accumulation in the cochlear ducts, stria vascularis, andcochlearnerve,whichpreventsthemfromfunctioning efficiently.14 _{Inthepresent cases,theincidenceofTypeB} andCtympanogram wasdeterminedtobe high,in accor-dancewiththeliterature.AccordingtoYuLinetal.,while this rateis stated toreach 70%, the incidence of Type B tympanogramwasdeterminedas77.77%andtheincidence ofType C tympanogram wasdeterminedas 16.66%in the presentstudy,similarly. VTapplication isadvised tocases withsimilarclinicalfindingsindifferentclinicsaswell,just asinthe present study.However,a majority of thecases inthisstudy havehindered theirtreatments,duetotheir families’rejectionoftheVTapplication.Incasesforwhich hearingaidsareadvised,whilesocio-economicalinadequacy creates hardships in coming to follow-ups and obtaining theseaids,the factthatmanylivein differentcities pre-ventscontinuityinfollow-ups.

Conclusion

IncaseswithMPS,sincetheincidenceofhearinglossishigh, thehearinglossshouldbedeterminedinearlystages.After the diagnosis, the required treatments should be started promptlyandthusqualityoflifeshouldbeincreased. How-ever,itisconsideredthatthisisonlypossibleasaresultof regularandsystematicfollow-upsandwithmultidisciplinary studies.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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