•DescriptionofBarthsyndrome

•Importantclinicalproblems

•Howtodiagnose

•Inheritance

•Highlightsofcurrentclinicalknowledge

•Resourcesforphysiciansandfamilies

What’s Inside

Do You Know About

Barth Syndrome?

Our lives depend on it!

www.barthsyndrome.org

Levi(age1)

Ben(age8)

Bryn(18months)

Christopher(age5)

Jeremiah(age15)

Andrew(age24)

Connor (age 3)

Barth syndrome (BTHS; OMIM #302060) is a rare, life-threatening genetic disorder primarily affecting males around the world. It is caused by a mutation in the tafazzin gene (TAZ, also called G4.5), resulting in an inborn error of lipid metabolism.

Thoughnot alwayspresent, cardinal characteristics of thismulti-systemdisorderoftenincludecombinationsandvaryingdegreesof:

• Cardiomyopathy(Usuallydilatedwithvariablemyocardialhypertrophy,sometimeswithleftventricularnoncompactionand/orendocardialfibroelastosis)

•Neutropenia(Chronic,cyclic,orintermittent)

•Underdeveloped skeletal musculature and muscle weakness

• Growth delay(Growthpatternsimilartobutoftenmoreseverethanconstitutionalgrowthdelay)

• Exercise intolerance

• Cardiolipin abnormalities

• 3-methylglutaconic aciduria (Typicallya5-to20-foldincrease)

What is Barth Syndrome?

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• Congestiveheartfailure

• Life-threateningbacterialinfection

• Grossmotordelay

• Riskoffatalarrhythmia

• Shortstatureintheearlyyears,followedbyacceleratedgrowthinmid-tolatepuberty

• Extremefatigue

• Diarrheaand/orconstipation

• Feedingproblems(e.g.,difficultysucking,swallowing,orchewing;aversiontosomefoodtextures;selectiveorpickyeating)

• Recurrentmouthulcers

• Riskofthrombosis

• Diminishedcapacityforexercise

• Hypoglycemia,includingfastinghypoglycemia(especiallyinthenewbornperiod)

• Chronicheadache,abdominalpain,and/orbodyaches(especiallyduringpuberty)

• Osteoporosis

• Somemildlearningdisabilities

Important Clinical Problems May Include (in varying severity):

Devin(age9)andHenry(age5).

Will(age27)andJohn(age31)atBSF’s2012Conference.

“The Barth Syndrome Foundation has saved my life due to some clinical information that was shared through the organization. Beyond the clinical impact that the BSF has had on my life, the foundation has also been a haven of understanding and social support as well as providing a built-in group of friends.” ~ Will, age 27, Affected Individual

(Photo courtesy BSF ~ 2012)

(Photo courtesy BSF ~ 2013)

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Phases of Barth Syndrome These general phases are often, but not always, seen in Barth syndrome:

• ChildrenwithBarthsyndromeoftenareseriouslyillbeforetheageoffiveyears.

• Theagesfromfivetoelevenyearscanbea“honeymoonphase,”whensymptomstypicallyimproveandpatientstendtobecrisis-free.

• Thisdoesnotmeanthatthesyndromehasbeen“outgrown.”Adolescenceoftenbeginsanotherdifficultperiod.

Despite these general phases, the following serious risks ALWAYS exist:

Risks of Cardiac Dysfunction •ThenaturalhistoryofBarthsyndromecardiacdiseasehasbeendescribedas “undulating.”Both the character andseverityofheartdysfunctioncanchangesignificantly.Thecardiomyopathy canevolve fromhypertrophic todilatedorviceversa,andmayormaynotinvolveleftventricularnoncompaction(LVNC).Furthermore,sometimesapatientsickenoughtobeawaitingahearttransplantcanimprovedramaticallyenoughtobetakenoffthelist,especiallyiftheunderlyingmetabolicabnormalitieshavebeentreatedandimproved.Unfortunately,thereversealsocanhappen,andheart functioncandeterioratesignificantly, suddenlyandunexpectedly,evenduringotherwisesimpleviralorbacterialinfections.Vigilantcardiacmonitoringisessential.

• Life-threateningarrhythmias canoccur,evenwhenheartfunctionisinthenormalrange.

Risks of Infection• Whenwell,aBarthsyndromeindividualcanhaveanabsoluteneutrophilcount(ANC)approachingzero,butthiscanrisetonormaloraboveduringanacuteinfection.Thus,therearetimeswhenanormalANCcanbeasignofa seriousinfection.

•ManywithBarthsyndromehaveanormalbodytemperaturethatissubstantiallybelow98.6°F(37°C),soevenamildfevermaysignifyaproblem.

• Takingarectaltemperatureiscontra-indicatedduetoriskofseriousinfection.

A Multi-System DisorderIt is critical always to remember that Barth syndrome (BTHS) is a complex inborn error of metabolism. It affects many systems of the body, so treating a patient with Barth syndrome often requires involvement of experts from a wide range of medical specialties.

Risks of Nutritional and Metabolic IssuesThe intrinsically reducedmusclemassofBarth syndrome•individuals significantly limits their ability to fast. Evenovernight fastingdrainsmuscle reserves, causing relativehypoglycemiaand,overtime,furthermuscleatrophy.Eatingcornstarch (e.g., added to yogurt)orExtendBars™beforebedtimecanalleviatetheseproblems.

Barthsyndromeindividualstendtotolerateillnessespoorly,•especiallythosethatincludediarrheaorvomiting,giventhatthere is reducedmusclemassand,asa result,diminishedbodystoresofelectrolytesandprotein.Therefore,fluidandelectrolyte (particularlypotassiumandphosphate)balancemustbemonitored closelyand frequentlyduring illnessesandcautionexercisedtopreventhyperkalemiawhengivingpotassium-containingIVfluids.Underlyingcardiacissuesalsomustbeconsideredinallofthis.

RarebutserioushypoglycemiccriseshaveoccurredinBarth•syndrome,soanysymptomsoflowbloodsugar(weakness,pallororsweating)mustbetakenseriously.

Thereisincreasingevidencethatthemetabolicstrategiesused•byBarthsyndromecellstomaintainnormalenergyproductionmaycausesufficientlyseveredepletionofcertainaminoacids,mostnotablyarginine,thatcardiacandskeletalmuscleproteinsynthesisisimpaired.Asaresult,theuseofextradietaryproteinand supplementsof arginineandotheraminoacidsmaybeconsideredtoraiseaminoacidlevelstotheirmid-normalrangesandtherebyreverseseriousdeterioration incardiac functioncausedbycardiacmusclewasting.

Anesthesia for Barth syndrome patients requires special•considerations due to increased risks from the cardiac,muscularandmetabolicissuesinvolvedinthedisorder.Dilatedcardiomyopathy is frequentlypresent, the riskof ventriculararrhythmiasiselevated,andlacticacidmayaccumulaterapidly.ThemuchreducedmusclemassofBarthsyndromecanleadtorapidelectrolyteshiftsandpredisposeBarthsyndromepatientstohypoglycemia.Thus,careshouldbetakentominimizefastingandtoavoiduseoflactatedintravenousfluids.

Barth syndrome (BTHS) patients often have a team of specialists potentially including:

A Multi-Disciplinary Approach

• Biochemicalgeneticist• Cardiologist• Clinicalgeneticist• Endocrinologist• Gastroenterologist• GeneralPhysician• Hematologist

• Immunologist• Neurologist• Nurses• Nutritionist• PhysicalTherapist• OccupationalTherapist• Andothers

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How to DiagnoseBarth syndrome (BTHS) is a complex, multi-system disorder. It can be difficult to recognize because all manifestations may not be simultaneously present or apparent.

ThediagnosisofBarth syndromeshouldbeconsidered forachildor adult presentingwith anyoneof its seven cardinalcharacteristicsorincaseswithfamilyhistoriesofmultiplemaledeathsorfetalloss.AlsonotethatafemaleBarthsyndromecasenowhasbeenreported.

Diagnostic Testing• DNAsequenceanalysis(genetictesting)ofthe tafazzin

gene(TAZ, alsocalledG4.5)

• Cardiolipinanalysisofvariouscellsandtissues

Lack of family history does not exclude the diagnosis of Barth syndrome, as there is a relatively high frequency of new mutations.

For more details about these tests, please visit GeneTests™:

www.genetests.org

Barth syndrome is an X-linked genetic condition, usuallytransmittedfrommothertoson(althoughthereisarelativelyhigh incidenceofnewmutations inBarth syndromeandoneconfirmedcasereportofafemaleBarthsyndromepatient).AmotherwhoisacarrierofaBarthsyndromemutation(thegeneisnamed tafazzin—also calledTAZ orG4.5) showsno signsorsymptomsofthisdisorderherself,probablyduetoskewedX-chromosomeinactivation.

Thereisa50%chancethataboyborntoafemalecarrierwillhaveBarthsyndrome,whereasgirlsborntoacarrierhavea50%riskofbeingcarriersthemselves.AlldaughtersofamalewithBarthsyndromewillbecarriers,howevernosonswillbeaffected.Becausethereareprovennon-carriermothers,allmothersofBarthsyndromechildrenshouldbetestedinordertodefinethegeneticriskineachfamily.

AnymalechildrelatedthroughthefemalelinetoaBarthsyndromeindividualshouldbetestedforthedisorder,astherecanbegreatvariationinphenotypeevenamongaffectedsiblings.

Inheritance

“Please consider this disease in any boy with cardiomyopathy of any form, muscle weakness, neutropenia or hypoglycemia, or in any family with a history of multiple male deaths in childhood or male fetal loss and still birth.” ~ Colin Steward, PhD, FRCP, FRCPCH, Pediatric Hematology, Bristol Royal Hospital for Children, Bristol, England

Dr.ColinStewardatBSF’s2012Conference.

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Brayden(age3)andTracy.

“The Barth Syndrome Foundation has been wonderful to us. I have met and gained friendships with people who are miles away. The information and support that you gain is amazing!”~Tracy, Mom

(Photo courtesy Birds Nest Foundation ~ 2013)

1998Female carriers of Barth syndrome asymptomatic due to X-chromosome inactivation.OrstavikKH,OrstavikRE,NaumovaAK,D´AdamoP,GedeonA,BolhuisPA,BarthPG,TonioloD.X-chromosomeinactivationincarriersofBarthsyndrome.AmJHumGenet1998Nov;63(5):1457-63.

1999Higher-than-expected unrelated Barth syndrome cases discovered in one hospital in Bristol, UK, indicating an under-diagnosis of this disease. CantlayAM,ShokrollahiK,AllenJT,LuntPW,Newbury-EcobRA,StewardCG.GeneticanalysisoftheG4.5geneinfamilieswithsuspectedBarthsyndrome.JPediatr1999Sep;135(3):311-15.ErratuminJPediatr2000Jun;136(1):136.

2001Clinical course and treatment of neutropenia in Barth syndrome patients presented.ZeidlerC,BarthPG,BonillaMA,BolyardAA,BoxerL,CottleT,DaleDC,DonadieuJ,FierC,FreedmanM,KannourakisG,KinseyS,LiangB,SchwinzerB,WelteK,ChamB,fortheSevereChronicNeutropeniaInternationalRegistry(SCNIR).NeutropeniainBarthsyndrome:Clinicalcourseandtreatmentofneutropenia.Blood2001;98(11):300a.

2003Phospholipid abnormalities documented in children with Barth syndrome.SchlameM,KelleyRI,FeigenbaumA,TowbinJA,HeerdtPM,SchliebleT,WandersRJ,DiMauroS,BlanckTJ.PhospholipidabnormalitiesinchildrenwithBarthsyndrome.JAmCollCardiol2003Dec3;42(11):1994-99.

2005Risk of serious arrhythmias and sudden cardiac death documented in adolescent Barth syndrome patients.SpencerCT,ByrneBJ,GewitzMH,WechslerSB,KaoAC,GerstenfeldEP,MerlissAD,CarboniMP,BryantRM.VentriculararrhythmiaintheX-linkedcardiomyopathyBarthsyndrome.PediatrCardiol.2005Sep-Oct;26(5):632-7.

2006Barth syndrome clinical phenotype described based on data from largest cohort of Barth syndrome patients to date.SpencerCT,BryantRM,DayJ,GonzalezIL,ColanSD,ThompsonWR,BerthyJ,RedfearnSP,ByrneBJ.CardiacandclinicalphenotypeinBarthsyndrome.Pediatrics2006Aug;118(2):e337-46.*

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Highlights of Current Clinical Knowledge

*PublicationsthatacknowledgefinancialsupportcontributedbyBarthSyndromeFoundation(BSF)and/orBSFaffiliates.

�Publicationsthatacknowledgebiologicalsamples(and/orinformation)fromBarthsyndromefamilies,theBarthSyndromeRegistryandRepository(BRR),and/orBSFaffiliates.

Bluehighlights:Publicationsthatmaybemostrelevantinanemergentsituation.

Forthemostup-to-dateinformation,includingafullBarthsyndrome(BTHS)bibliographyandlinkstoPubMedabstracts,pleasevisitwww.barthsyndrome.org.

1981 and 1983 An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. First mentioned in 1981, and then fully described in 1983 by Dr. Peter Barth (pediatric neurologist).BarthPG,ScholteHR,BerdenJA,VanderKlei-VanMoorselJM,Luyt-HouwenIE,VantVeer-KorthofET,VanderHartenJJ,Sobotka-PlojharMA.AnX-linkedmitochondrialdiseaseaffectingcardiacmuscle,skeletalmuscleandneutrophilleucocytes.JNeurSci1983Dec;62(1-3):327-55.

1991 3-methylglutaconic aciduria found to be a clinical biochemical marker for Barth syndrome.KelleyRI,CheathamJP,ClarkBJ,NigroMA,PowellBR,SherwoodGW,SladkyJT,SwisherWP.X-linkeddilatedcardiomyopathywithneutropenia,growthretardationand3-methylglutaconicaciduria.JPediatr1991;119(5):738-47.

1995 G-CSF used successfully to treat neutropenia in Barth syndrome. CoxGF,PulsipherM,RothenbergM,KorsonM,KelleyRI.CorrectionofneutropeniainBarthsyndromebyG-CSF.AmJHumGenet1995;57(Suppl):A177.

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“The cruelest irony about Barth syndrome is how deceptively healthy those who have it may appear. A casual observer would never appreciate them to have such a devastating illness.” ~ Peter Barth, MD, PhD, Pediatric Neurology (retired), Emma Children’s Hospital/Academic Medical Center, Amsterdam, The Netherlands

2007Successful cardiac transplantation in Barth syndrome and detailed experience with specific post-transplant medications discussed.MangatJ,Lunnon-WoodT,ReesP,ElliottM,BurchM.SuccessfulcardiactransplantationinBarthsyndrome:Single-centreexperienceoffourpatients.PediatrTransplant2007May;11(3):327-31.

2008Barth syndrome screening using bloodspots and HPLC tandem mass spectrometry developed. KulikW,vanLentheH,StetFS,HoutkooperRH,KempH,StoneJE,StewardCG,WandersRJ,VazFM.BloodspotassayusingHPLCtandemmassspectrometryfordetectionofBarthsyndrome.ClinChem.2008Feb;54(2):371-8.Epub2007Dec10.*

2009Quality of life for youth with Barth syndrome lower than that for healthy individuals and for those with cardiac disease alone. StorchEA,KeeleyM,MerloLJ,St.AmantJB,JacobM,StorchJ,SpencerC,ByrneBB.PsychosocialfunctioninginyouthwithBarthsyndrome.Children’sHealthCare.2009Apr;38(2):137-56.*

Common childhood Barth syndrome facial features include tall and broad forehead, round face, prominent chin, full cheeks, large ears and deep-set eyes. Gynoid stature and fat distribution often develop in late puberty.HastingsR,StewardC,Tsai-GoodmanB,Newbury-EcobR.DysmorphologyofBarthsyndrome.ClinDysmorphol.2009Oct;18(4):185-7.*

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2010First conclusive demonstration given that Barth syndrome can cause male fetal loss and stillbirth in multiple families.StewardCG,Newbury-EcobRA,HastingsR,SmithsonSF,Tsai-GoodmanB,QuarrellOW,KulikW,WandersR,PennockM,WilliamsM,CresswellJL,GonzalezIL,BrennanP.Barthsyndrome:AnX-linkedcauseoffetalcardiomyopathyandstillbirth.PrenatDiagn.2010Oct;30(10):970-6.*�

2011Severe exercise intolerance in Barth syndrome due to cardiac and skeletal muscle impairments consistent with cardiac and skeletal mitochondrial myopathy. SpencerCT,ByrneBJ,BryantRM,MargossianR,MaisenbacherM,BreitengerP,BenniPB,RedfearnS,MarcusE,CadeWT.ImpairedcardiacreserveandseverelydiminishedskeletalmuscleoxygenutilizationmediateexerciseintoleranceinBarthsyndrome.AmJPhysiolHeartCircPhysiol.2011Nov;301(5):H2122-9.Epub2011Aug26.*�

2012First case report of female Barth syndrome patient confirmed by genetic analysis.CossonL,ToutainA,SimardG,PaoliF,KulikW,VazFM,BlascoH,ChantepieA,LabartheF.CossonL,ToutainA,SimardG,KulikW,MatyasG,GuichetA,BlascoH,Maakaroun-VermesseZ,VaillantMC,LeCaignecC,ChantepieA,LabartheF.Barthsyndromeinafemalepatient.MolGenetMetab.2012May;106(1):115-20.Epub2012Jan24.

Report of child with Barth syndrome and ‘‘undulating cardiac phenotype” who ultimately developed decompensated heart failure requiring mechanical circulatory support of ventricular assist device as bridge to transplantation. Course was complicated by acute lung injury requiring placement of in-line oxygenator to maintain end-organ function.HankeSP,GardnerAB,LombardiJP,ManningPB,NelsonDP,TowbinJA,JefferiesJL,LortsA.LeftventricularnoncompactioncardiomyopathyinBarthsyndrome:Anexampleofanundulatingcardiacphenotypenecessitatingmechanicalcirculatorysupportasabridgetotransplantation.PediatrCardiol.2012Dec;33(8):1430-4.Epub2012Mar17.

Highlights of Current Clinical Knowledge

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2012(cont’d)Report of family with novel TAZ mutation and clinical spectrum from severe Barth syndrome in infant to skeletal myopathy with LVNC in adult, the oldest individual with Barth syndrome reported.RonveliaD,GreenwoodJ,PlattJ,HakimS,ZaragozaMV.IntrafamilialvariabilityfornovelTAZgenemutation:Barthsyndromewithdilatedcardiomyopathyandheartfailureinaninfantandleftventricularnoncompactioninhisgreat-uncle.MolGenetMetab.2012Nov;107(3):428-32.Epub2012Sep18.

Review article detailing longitudinal data collected, including growth curves, from Barth Syndrome Registry and Repository. RobertsAE,NixonC,StewardCG,GauvreauK,MaisenbacherM,FletcherM,GevaJ,ByrneBJ,SpencerCT.TheBarthSyndromeRegistry:Distinguishingdiseasecharacteristicsandgrowthdatafromalongitudinalstudy.AmJMedGenetA.2012Nov;158A(11):2726-32.Epub2012Oct8.(Open Access)*�

2013Summary of clinically important information about Barth syndrome.JefferiesJL.Barthsyndrome.AmJMedGenetCSeminMedGenet.2013Aug;163(3):198-205.Epub2013Jul10.(Open Access)

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2012(cont’d)Tafazzin deficiency in mouse model of Barth syndrome leads to unique developmental cardiomyopathy characterized by ventricular myocardial hypertrabeculation-noncompaction and early lethality. Central role of cardiolipin and mitochondrial functioning strongly implicated in cardiomyocyte differentiation and myocardial patterning required for heart development.PhoonCKL,AcehanD,SchlameM,StokesDL,Edelman-NovemskyI,YuD,XuY,ViswanathanN,RenM.Tafazzin knockdowninmiceleadstoadevelopmentalcardiomyopathywithearlydiastolicdysfunctionprecedingmyocardialnoncompaction.JAmHeartAssoc.2012Apr;1(2).Epub2012Apr24.*�

Expanded upon existing knowledge of math difficulties reported for Barth syndrome individuals by evaluating the emergence, nature, and trajectory of mathematics difficulties in this population.RachesD,MazzoccoMM.EmergenceandnatureofmathematicaldifficultiesinyoungchildrenwithBarthsyndrome.JDevBehavPediatr.2012May;33(4):328-35.*�

Basic information that defines problems Barth syndrome individuals face every day — extreme fatigue and its relationship to heart function. We know that Barth syndrome individuals have problems with their heart (cardiomyopathy), however this paper shows that their fatigue also has to do with how muscle cells convert energy into movement. CadeWT,SpencerCT,ReedsDN,WaggonerAD,O’ConnorR,MaisenbacherM,CrowleyJR,ByrneBJ,PetersonLR.Substratemetabolismduringbasalandhyperinsulinemicconditionsinadolescentsandyoung-adultswithBarthsyndrome.JInheritMetabDis.2013Jan;36(1):91-101.Epub2012May12.*�

Study conducted to examine prevalence of atypical sensory processing in 21 boys with Barth syndrome and to explore if phenotypic patterns of sensory responsiveness may be useful in early diagnosis. Using mixed methods approach, they found that sensory issues related to feeding and eating were ubiquitous in our sample, with some behaviors such as strong gag reflex identifiable early in development.ReynoldsS,KreiderCM,BendixenR.Amixed-methodsinvestigationofsensoryresponsepatternsinBarthsyndrome:Aclinicalphenotype?AmJMedGenetPartA.7Jun2012Jul;158A(7):1647-53.*�

Highlights of Current Clinical Knowledge

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“The science presented at the Barth Syndrome Foundation 2012 Conference was incredible. I consider this among the most important work I have done in my career.” ~ Colin Phoon, MPhil, MD, New York University School of Medicine and Langone Medical Center, New York, New York

2013 (cont’d)Review of recent advances in understanding molecular and cellular bases of neutropenia in Barth syndrome.AprikyanAA,KhuchuaZ.AdvancesintheunderstandingofBarthsyndrome.BrJHaematol.2013May;161(3):330-8.Epub2013Feb25.�

Report from French historical experiences with Barth syndrome individuals and how good medical practices contributed to survival.RigaudC,LebreA,TouraineR,BeaupainB,OttolenghiC,ChabliA,AnsquerH,OzsahinH,DiFilippoS,DeLonlayP,BormB,RivierF,VaillantM,Mathieu-DramardM,GoldenbergA,ViotG,CharronP,RioM,BonnetD,DonadieuJ.NaturalhistoryofBarthsyndrome:Anationalcohortstudyof22patients.OrphanetJRareDis.2013May8;8:70.(Open Access)*�

Extended use of Berlin Heart EXCOR as bridge to transplant in 3-year old Barth syndrome individual.DedieuN,GiardiniA,StewardCG,FentonM,KarimovaA,HsiaTY,BurchM.Successfulmechanicalcirculatorysupportfor251daysinachildwithintermittentsevereneutropeniaduetoBarthsyndrome.PediatrTransplant.2013Mar;17(2):E46-9.Epub2012Nov28.�

Clinical report from Italian population detailing six Barth syndrome patients with five harboring new mutations in the tafazzin gene including three deletions.FerriL,DonatiMA,FunghiniS,MalvagiaS,CatarziS,LugliL,RagniL,BertiniE,VazFM,CooperDN,GuerriniRR,MorroneA.NewclinicalandmolecularinsightsonBarthsyndrome.OrphanetJRareDis.2013Feb14;8(1):27.doi:10.1186/1750-1172-8-27. �

Comprehensive review article about Barth syndrome.ClarkeSLN,BowronA,GonzalezIL,GrovesSJ,Newbury-EcobR,ClaytonN,MartinRP,Tsai-GoodmanB,GarrattV,AshworthM,BowenVM,McCurdyKR,DaminMK,SpencerCT,TothMJ,KelleyRI,StewardCG.Barthsyndrome.OrphanetJournalofRareDiseases2013,8:23.(Open Access)*�

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Highlights of Current Clinical Knowledge

Saving lives through education, advances in treatment, and finding a cure for Barth syndrome.

Our Mission is...

Raphaël, age 4.(Photo courtesy of Barth France ~ 2013)

“Interacting with organizations like BSF makes our work much more pleasant and gives us a sense of the collaborative effort to fulfill our goals.” ~ Yaffa Rubinstein, PhD, Director of Patient Resources for Clinical and Translational Research, Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health

2013(cont’d)Case report of two brothers with Barth syndrome demonstrating measurable defects in mitochondrial membrane potential but differing in severity of symptoms including neonatal 3-methylglutaconic aciduria and asymptomatic left ventricular non-compaction.Karkucinska-WieckowskaA,TrubickaJ,WernerB,KokoszynskaK,PajdowskaM,PronickiM,CzarnowskaE,LebiedzinskaM,Sykut-CegielskaJ,ZiolkowskaL,JaronW,DobrzanskaA,CiaraE,WieckowskiMR,PronickaE.Leftventricularnoncompaction(LVNC)andlowmitochondrialmembranepotentialarespecificforBarthsyndrome.JInheritMetabDis.2013Jan30.[Epubaheadofprint]

“Life before BSF can be characterized by one word, isolation. Isolation from informed doctors and researchers, from necessary services, from other affected boys and families, and from support of any nature. Life since BSF can be characterized by one word, teamwork. Teamwork amongst doctors and researchers, services providers, affected boys and their families, and support from all involved! BSF is HOPE, for a treatment, a cure, for a better life for all our boys/young men!” ~Rosemary, Mother

TheBarthSyndromeFoundation(BSF)anditsaffiliatesareagroupofinternationalnon-profitorganizationsthatprovideinformation,resourcesandservicesforhealthcareprofessionalsandfamiliesworldwide.Advising the group is aworld-class ScientificandMedicalAdvisoryBoard (SMAB), comprisedof clinicians andscientistswhoareleadingexpertsinBarthsyndrome.

BSF’s website(www.barthsyndrome.org)containsthemostup-to-dateeducationalmaterials and researchfindings, includingacomprehensiveon-linelibrarywhichservesboththemedicalcommunityandaffectedfamilies.

BSF’sInternational Barth Syndrome Conference,heldeverytwoyears,isreallytwosimultaneousmeetings.Onemeetingbringstogetherdoctorsandscientistsinvolvedinthemanyaspectsofthedisordertodiscussthelatestunderlyingscientificdevelopmentsandclinical insights; it isauniqueexperiencethatencouragescollaborationandaccelerates advances inunderstandingandtreatment. Theother is a familymeeting inwhich the latestinformationisdiscussedwithfamilies.Freeconsultationsessionsarealsoheldenablingfamiliestomeetwithmedicalexpertsfromaround theworld. In addition,opportunities toparticipate inresearchstudiesandprovideimportantclinicaldataandbiologicalsamples to theBarth SyndromeRegistry andRepository areofferedtoBarthsyndromeindividuals.

TheSci/Med ListservisanongoingforumwheremembersofourinternationalScientificandMedicalAdvisoryBoard,cliniciansandresearcherscollaborate,askquestionsandexchangethelatestinformation.

TheFamily Listservisaforumwherehealthcareprovidersandfamilies engage in opendiscussionson themany aspects ofthisdisorderanditstreatment. It isanimmediateeducationalresourceforfamilies.

Resources for Healthcare Providers and Families

Barth Syndrome Foundation

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Research Grant ProgramBSF and its affiliates sponsor a competitive research grantprogramtofacilitateadvancesinBarthsyndromeunderstandingand to encourage thediscovery of new treatments.Grantapplications are evaluatedbyBSF’s international ScientificandMedicalAdvisoryBoard,with input fromexpertoutsidereviewers.Over the past eleven years,we have awarded72 separate grants totaling almostUS $2.7Million, to 43investigatorsaroundtheworld.

Barth Syndrome Registry & RepositoryTheBarthSyndromeFoundation (BSF)hasbeen selected toparticipateinatwo-yearpilotprojectoftheNationalInstitutesofHealth (NIH) called theGlobalRareDiseaseRegistryandDataRepository(GRDR).Asapilotparticipant,BSFwillworkin collaborationwith leaders in rare disease research attheOffice of RareDiseases Research,National Center forAdvancingTranslationalSciences,NationalInstitutesofHealth,PatientCrossroads, Children’sHospital of Philadelphia, andWebMD.TheGRDRprogramwillcollectde-identifiedpatienthealthinformationfromparticipatingregistriesestablishedbyindividualrarediseaseorganizationsinordertoallowanalysesofdataacrossmanyrarediseasesaswellastofacilitateclinicaltrialsandotherstudies.ThisGRDRprogrambuildsonourexistingRegistry&Repositoryandhasbeenestablishedtopromotethecollectionandsharingofclinicalhistoriesandbiologicalsamples(includingcelllines)ofBarthsyndromepatients.TheRegistry&Repositoryareavailabletoanyqualifiedresearcher,worldwide,whoisinterestedinstudyingBarthsyndrome.Foradirectlink,pleasevisitthehomepageofBSF’swebsite.

Human Tafazzin Gene Mutation & Variation DatabaseA central, up-to-date database listing all knownmutationsandvariationsinthehumantafazzin(TAZ orG4.5)genewasestablishedbyandismaintainedbyBSF.Thisisaveryvaluableresourcewhich can be easily accessed through ourmainwebsite.Westronglyencourageanyonewhoknowsofanewcase(evenifitinvolvesamutationorvariationthatisalreadylisted)tocontactthelistmasterforinclusioninthisdatabase.

Forfurtherinformationonourresearchprograms,pleasevisitourwebsiteatwww.barthsyndrome.org.

Resources for Barth Syndrome Research

I’m quite certain it is under-diagnosed. If you have never heard of the disease, you are not going to look, you are not going to find. ~Jeffrey Towbin, MD, FAAP, FACC, FAHA, Chief, Pediatric Cardiology, Cincinnati Children’s Hospital, Cincinnati, Ohio

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Please Join Us•JoinBSFatnocost.

•Bekeptup-to-dateonthelatesteducationalmaterialsandresearchfindings.

•Gainaccesstoandparticipateininformativelistservstocollaborateandshareinformation.

•Receiveanadvanceinvitationtoourmulti-trackInternationalScientific,MedicalandFamilyConferenceheldeverytwoyears(withthenextscheduledforlateJune2014inClearwater,Florida).PleasevisitBSF’swebsiteforadditionalinformation.

•ParticipateintheBarthSyndromeRegistry&Repositorytofurtherresearch.Foradirectlink,pleasevisitthehomepageofBSF’swebsite(www.barthsyndrome.org).

•Receiveournewsletterwhichdeliversrelevantandtimelyresearch,medical,andorganizationalinformation.

Please contact us for more information.

bsfinfo@barthsyndrome.org

“My attendance at BSF’s conference was invaluable in learning about patients with this disorder and about scientific progress into the mechanisms of disease and genotype-phenotype correlations.”~ Arnold W. Strauss, MD, BK Rachford Professor and Chair, Department of Pediatrics, University of Cincinnati College of Medicine; Director, Cincinnati Children’s Research Foundation; Chief Medical Officer, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Aiden(age2)

Bly(age9)

Noah(age11)

R.J.(age15)

Kevin(age24)

Barth Syndrome Foundation, Inc.POBox618Larchmont,NewYork10538Telephone:(850)273-6947Fascimile:(518)213-4061E-mail:bsfinfo@barthsyndrome.orgWebsite:www.barthsyndrome.org

Affiliates

Association Barth France12,rueLalo75116ParisFranceTelephone:+33145008612E-Mail:associationbarthfrance@orange.frWebsite:http://www.barthfrance.com

Barth Syndrome Trust (UnitedKingdom&Europe)1TheVikingsRomseyHampshireS0515RGUnitedKingdomTelephone:+44(0)1794518785E-mail:info@barthsyndrome.org.ukWebsite:www.barthsyndrome.org.uk

Barth Syndrome Foundation of Canada162GuelphStreetSuite115Georgetown,ONL7G5X7CanadaTelephone:(905)873-2391E-mail:inquiries@barthsyndrome.caWebsite:www.barthsyndrome.ca

Barth Trust of South Africa49AbeliaRoadKloof,Pinetown3610NatalSouthAfricaTelephone:082-465-1965E-mail:jthorpe@barthsyndrome.orgWebsite:www.barthsyndrome.org/South_Africa.html

www.barthsyndrome.org

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Michael Schlame, MD – Chairman CellBiology&Anesthesiology,NewYorkUniversitySchoolofMedicine,NewYork,NewYork

Peter G. Barth, MD, PhD – EmeritusPediatricNeurology(retired), EmmaChildren’sHospital/AcademicMedicalCenter,Amsterdam,TheNetherlands

W. Todd Cade, PT, PhDPhysicalTherapy&InternalMedicine,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri

Gerald F. Cox, MD, PhDClinicalGenetics,Children’sHospital,Boston,Massachusetts;ClinicalResearch,GenzymeCorp.,Cambridge,Massachusetts

Iris L. Gonzalez, PhDMolecularDiagnosticsLab(retired), A.I.duPontHospitalforChildren,Wilmington,Delaware

Miriam L. Greenberg, PhDBiologicalSciences,WayneStateUniversity,Detroit,Michigan

Grant M. Hatch, PhDLipidLipoproteinResearch,UniversityofManitoba,Winnipeg,Canada

Richard I. Kelley, MD, PhDDivisionofMetabolism,KennedyKriegerInstitute,JohnsHopkinsUniversity,Baltimore,Maryland

William T. Pu, MDPediatricCardiology,BostonChildren’sHospital;HarvardStemCellInstitute,Boston,Massachusetts

Mindong Ren, PhDCellBiology,NewYorkUniversitySchool,ofMedicine,NewYork,NewYork

Colin G. Steward, PhD, FRCP, FRCPCHPediatricHematology,BristolRoyalHospitalforChildren,Bristol,England

Arnold Strauss, MDPediatricsandResearch,CincinnatiChildren’sHospitalMedicalCenter;CincinnatiChildren’sResearchFoundation,Cincinnati,Ohio

Jeffrey A. Towbin, MDPediatricCardiology,CincinnatiChildren’sHospitalMedicalCenter&UniversityofCincinnati,Cincinnati,Ohio

Ronald J. A. Wanders, PhDGeneticMetabolicDiseases,AcademicMedicalCenter,Amsterdam,TheNetherlands

Katherine R. McCurdy – ex-officio BoardMember,BarthSyndromeFoundation,Inc.

Matthew J. Toth, PhD –ex-officio ScienceDirector,BarthSyndromeFoundation,Inc.

Reviewed by SMAB Clinical MembersHealthcareProfessionalBrochure~October2013

www.barthsyndrome.org

Barth Syndrome FoundationInternational Scientifc and Medical

Advisory Board