Professional Healthcare Brochure

Do You
Know About
Barth Syndrome?
Levi (age 1)
Bryn (18 months)
Christopher (age 5)
Connor (age 3)
What’s Inside
Ben (age 8)
•Description of Barth syndrome
•Important clinical problems
•How to diagnose
Jeremiah (age 15)
•Inheritance
•Highlights of current clinical
knowledge
•Resources for physicians and
families
Our lives
depend on it!
Andrew (age 24)
www.barthsyndrome.org
What is Barth Syndrome?
Important Clinical Problems
May Include (in varying severity):
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.
• Congestive heart failure
Though not always present, cardinal characteristics of this
multi-system disorder often include combinations and varying
degrees of:
• Risk of fatal arrhythmia
• Cardiomyopathy
(Usually dilated with variable myocardial hypertrophy,
sometimes with left ventricular noncompaction and/or
endocardial fibroelastosis)
• Neutropenia
(Chronic, cyclic, or intermittent)
• Underdeveloped skeletal musculature and muscle
weakness
• Life-threatening bacterial infection
• Gross motor delay
• Short stature in the early years, followed by accelerated
growth in mid- to late puberty
• Extreme fatigue
• Diarrhea and/or constipation
• Feeding problems (e.g., difficulty sucking, swallowing, or chewing; aversion to some food textures; selective
or picky eating)
• Recurrent mouth ulcers
• Risk of thrombosis
• Growth delay (Growth pattern similar to but often more severe than
constitutional growth delay)
• Diminished capacity for exercise
• Exercise intolerance
• Chronic headache, abdominal pain, and/or body aches
(especially during puberty)
• Cardiolipin abnormalities
• 3-methylglutaconic aciduria
(Typically a 5- to 20-fold increase)
• Hypoglycemia, including fasting hypoglycemia (especially in the newborn period)
• Osteoporosis
• Some mild learning disabilities
(Photo courtesy BSF ~ 2012)
Will (age 27) and John (age 31) at BSF’s 2012 Conference.
(Photo courtesy BSF ~ 2013)
Devin (age 9) and Henry (age 5).
Page 2
“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
Page 3
A Multi-System Disorder
It 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.
Phases of Barth Syndrome These general phases are often, but not always, seen in
Barth syndrome:
• Children with Barth syndrome often are seriously ill before
the age of five years.
• The ages from five to eleven years can be a “honeymoon
phase,” when symptoms typically improve and patients tend
to be crisis-free.
• This does not mean that the syndrome has been “outgrown.”
Adolescence often begins another difficult period.
Despite these general phases, the following serious risks
ALWAYS exist:
Risks of Cardiac Dysfunction
• The natural history of Barth syndrome cardiac disease has
been described as “undulating.” Both the character and
severity of heart dysfunction can change significantly. The
cardiomyopathy can evolve from hypertrophic to dilated
or vice versa, and may or may not involve left ventricular
noncompaction (LVNC). Furthermore, sometimes a patient
sick enough to be awaiting a heart transplant can improve
dramatically enough to be taken off the list, especially if the
underlying metabolic abnormalities have been treated and
improved. Unfortunately, the reverse also can happen, and
heart function can deteriorate significantly, suddenly and
unexpectedly, even during otherwise simple viral or bacterial
infections. Vigilant cardiac monitoring is essential.
• Life-threatening arrhythmias can occur, even when heart
function is in the normal range.
Risks of Infection
• When well, a Barth syndrome individual can have an absolute
neutrophil count (ANC) approaching zero, but this can rise
to normal or above during an acute infection. Thus, there
are times when a normal ANC can be a sign of a serious
infection.
• Many with Barth syndrome have a normal body temperature
that is substantially below 98.6°F (37°C), so even a mild fever
may signify a problem.
• Taking a rectal temperature is contra-indicated due to risk
of serious infection.
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Risks of Nutritional and Metabolic Issues
• The intrinsically reduced muscle mass of Barth syndrome
individuals significantly limits their ability to fast. Even
overnight fasting drains muscle reserves, causing relative
hypoglycemia and, over time, further muscle atrophy. Eating
cornstarch (e.g., added to yogurt) or Extend Bars™ before
bedtime can alleviate these problems.
• Barth syndrome individuals tend to tolerate illnesses poorly,
especially those that include diarrhea or vomiting, given that
there is reduced muscle mass and, as a result, diminished
body stores of electrolytes and protein. Therefore, fluid and
electrolyte (particularly potassium and phosphate) balance
must be monitored closely and frequently during illnesses
and caution exercised to prevent hyperkalemia when giving
potassium-containing IV fluids. Underlying cardiac issues also
must be considered in all of this.
• Rare but serious hypoglycemic crises have occurred in Barth
syndrome, so any symptoms of low blood sugar (weakness,
pallor or sweating) must be taken seriously.
• There is increasing evidence that the metabolic strategies used
by Barth syndrome cells to maintain normal energy production
may cause sufficiently severe depletion of certain amino acids,
most notably arginine, that cardiac and skeletal muscle protein
synthesis is impaired. As a result, the use of extra dietary protein
and supplements of arginine and other amino acids may be
considered to raise amino acid levels to their mid-normal ranges
and thereby reverse serious deterioration in cardiac function
caused by cardiac muscle wasting.
• Anesthesia for Barth syndrome patients requires special
considerations due to increased risks from the cardiac,
muscular and metabolic issues involved in the disorder. Dilated
cardiomyopathy is frequently present, the risk of ventricular
arrhythmias is elevated, and lactic acid may accumulate rapidly.
The much reduced muscle mass of Barth syndrome can lead to
rapid electrolyte shifts and predispose Barth syndrome patients
to hypoglycemia. Thus, care should be taken to minimize fasting
and to avoid use of lactated intravenous fluids.
A Multi-Disciplinary Approach
Barth syndrome (BTHS) patients often have a team of specialists
potentially including:
• Biochemical geneticist
• Immunologist
• Cardiologist
• Neurologist
• Clinical geneticist
• Nurses
• Endocrinologist
• Nutritionist
• Gastroenterologist
• Physical Therapist
• General Physician
• Occupational Therapist
• Hematologist
• And others
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How to Diagnose
(Photo courtesy Birds Nest Foundation ~ 2013)
Barth syndrome (BTHS) is a complex, multi-system disorder.
It can be difficult to recognize because all manifestations may
not be simultaneously present or apparent.
The diagnosis of Barth syndrome should be considered for a
child or adult presenting with any one of its seven cardinal
characteristics or in cases with family histories of multiple male
deaths or fetal loss. Also note that a female Barth syndrome case
now has been reported.
Diagnostic Testing
• DNA sequence analysis (genetic testing) of the tafazzin
gene (TAZ, also called G4.5)
• Cardiolipin analysis of various cells and tissues
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
Brayden (age 3) and Tracy.
“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
(Photos courtesy BSF)
Inheritance
Dr. Colin Steward at BSF’s 2012 Conference.
“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
Page 6
Barth syndrome is an X-linked genetic condition, usually
transmitted from mother to son (although there is a relatively
high incidence of new mutations in Barth syndrome and one
confirmed case report of a female Barth syndrome patient). A
mother who is a carrier of a Barth syndrome mutation (the gene
is named tafazzin — also called TAZ or G4.5) shows no signs
or symptoms of this disorder herself, probably due to skewed
X-chromosome inactivation.
There is a 50% chance that a boy born to a female carrier will
have Barth syndrome, whereas girls born to a carrier have a 50%
risk of being carriers themselves. All daughters of a male with
Barth syndrome will be carriers, however no sons will be affected.
Because there are proven non-carrier mothers, all mothers of
Barth syndrome children should be tested in order to define the
genetic risk in each family.
Any male child related through the female line to a Barth syndrome
individual should be tested for the disorder, as there can be great
variation in phenotype even among affected siblings.
Page 7
Highlights of Current Clinical Knowledge
* Publications that acknowledge financial support contributed
by Barth Syndrome Foundation (BSF) and/or BSF affiliates.
� Publications that acknowledge biological samples (and/
or information) from Barth syndrome families, the Barth
Syndrome Registry and Repository (BRR), and/or BSF
affiliates.
Blue highlights: Publications that may be most relevant in an
emergent situation.
For the most up-to-date information, including a full Barth
syndrome (BTHS) bibliography and links to PubMed abstracts,
please visit www.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). Barth PG, Scholte HR, Berden JA, Van der Klei-Van Moorsel
JM, Luyt-Houwen IE, Van tVeer-Korthof ET, Van der Harten
JJ, Sobotka-Plojhar MA. An X-linked mitochondrial disease
affecting cardiac muscle, skeletal muscle and neutrophil
leucocytes. J Neur Sci 1983 Dec;62(1-3):327-55.
1998
Female carriers of Barth syndrome asymptomatic due to
X-chromosome inactivation.
Orstavik KH, Orstavik RE, Naumova AK, D´Adamo P,
Gedeon A, Bolhuis PA, Barth PG, Toniolo D. X-chromosome
inactivation in carriers of Barth syndrome. Am J Hum Genet
1998 Nov;63(5):1457-63.
1999
Higher-than-expected unrelated Barth syndrome cases
discovered in one hospital in Bristol, UK, indicating an
under-diagnosis of this disease.
Cantlay AM, Shokrollahi K, Allen JT, Lunt PW, Newbury-Ecob
RA, Steward CG. Genetic analysis of the G4.5 gene in families
with suspected Barth syndrome. J Pediatr 1999 Sep;135(3):
311-15. Erratum in J Pediatr 2000 Jun;136(1):136.
2001
Clinical course and treatment of neutropenia in Barth
syndrome patients presented.
Zeidler C, Barth PG, Bonilla MA, Bolyard AA, Boxer L, Cottle
T, Dale DC, Donadieu J, Fier C, Freedman M, Kannourakis
G, Kinsey S, Liang B, Schwinzer B, Welte K, Cham B, for the
Severe Chronic Neutropenia International Registry (SCNIR).
Neutropenia in Barth syndrome: Clinical course and
treatment of neutropenia. Blood 2001; 98(11):300a.
1991
3-methylglutaconic aciduria found to be a clinical biochemical
marker for Barth syndrome.
Kelley RI, Cheatham JP, Clark BJ, Nigro MA, Powell BR,
Sherwood GW, Sladky JT, Swisher WP. X-linked dilated
cardiomyopathy with neutropenia, growth retardation and
3-methylglutaconic aciduria. J Pediatr 1991;119(5):738-47.
2003
Phospholipid abnormalities documented in children with
Barth syndrome.
Schlame M, Kelley RI, Feigenbaum A, Towbin JA, Heerdt
PM, Schlieble T, Wanders RJ, DiMauro S, Blanck TJ.
Phospholipid abnormalities in children with Barth
syndrome. J Am Coll Cardiol 2003 Dec 3;42(11):1994-99.
1995
G-CSF used successfully to treat neutropenia in Barth syndrome.
Cox GF, Pulsipher M, Rothenberg M, Korson M, Kelley RI.
Correction of neutropenia in Barth syndrome by G-CSF. Am
J Hum Genet 1995; 57(Suppl):A177.
2005
Risk of serious arrhythmias and sudden cardiac death
documented in adolescent Barth syndrome patients.
Spencer CT, Byrne BJ, Gewitz MH, Wechsler SB, Kao AC,
Gerstenfeld EP, Merliss AD, Carboni MP, Bryant RM.
Ventricular arrhythmia in the X-linked cardiomyopathy
Barth syndrome. Pediatr Cardiol. 2005 Sep-Oct;26(5):632-7.
“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
Page 8
2006
Barth syndrome clinical phenotype described based on data
from largest cohort of Barth syndrome patients to date.
Spencer CT, Bryant RM, Day J, Gonzalez IL, Colan SD,
Thompson WR, Berthy J, Redfearn SP, Byrne BJ. Cardiac
and clinical phenotype in Barth syndrome. Pediatrics 2006
Aug;118(2):e337-46.*
Page 9
Highlights of Current Clinical Knowledge
2007
Successful cardiac transplantation in Barth syndrome
and detailed experience with specific post-transplant
medications discussed.
Mangat J, Lunnon-Wood T, Rees P, Elliott M, Burch M.
Successful cardiac transplantation in Barth syndrome:
Single-centre experience of four patients. Pediatr
Transplant 2007 May;11(3):327-31.
2008
Barth syndrome screening using bloodspots and HPLC
tandem mass spectrometry developed.
Kulik W, van Lenthe H, Stet FS, Houtkooper RH, Kemp H,
Stone JE, Steward CG, Wanders RJ, Vaz FM. Bloodspot assay
using HPLC tandem mass spectrometry for detection of
Barth syndrome. Clin Chem. 2008 Feb;54(2):371-8. Epub
2007 Dec 10.*
2009
Quality of life for youth with Barth syndrome lower than
that for healthy individuals and for those with cardiac
disease alone.
Storch EA, Keeley M, Merlo LJ, St. Amant JB, Jacob M,
Storch J, Spencer C, Byrne BB. Psychosocial functioning in
youth with Barth syndrome. Children’s Health Care. 2009
Apr;38(2):137-56.*
(Photo courtesy BSF ~ 2013)
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.
Hastings R, Steward C, Tsai-Goodman B, Newbury-Ecob R. Dysmorphology of Barth syndrome. Clin Dysmorphol. 2009
Oct;18(4):185-7.*
2010
First conclusive demonstration given that Barth syndrome
can cause male fetal loss and stillbirth in multiple families.
Steward CG, Newbury-Ecob RA, Hastings R, Smithson
SF, Tsai-Goodman B, Quarrell OW, Kulik W, Wanders
R, Pennock M, Williams M, Cresswell JL, Gonzalez IL,
Brennan P. Barth syndrome: An X-linked cause of fetal
cardiomyopathy and stillbirth. Prenat Diagn. 2010
Oct;30(10):970-6.*�
2011
Severe exercise intolerance in Barth syndrome due to
cardiac and skeletal muscle impairments consistent with
cardiac and skeletal mitochondrial myopathy.
Spencer CT, Byrne BJ, Bryant RM, Margossian R,
Maisenbacher M, Breitenger P, Benni PB, Redfearn S,
Marcus E, Cade WT. Impaired cardiac reserve and severely
diminished skeletal muscle oxygen utilization mediate
exercise intolerance in Barth syndrome. Am J Physiol Heart
Circ Physiol. 2011 Nov;301(5):H2122-9. Epub 2011 Aug 26.*�
2012
First case report of female Barth syndrome patient confirmed
by genetic analysis.
Cosson L, Toutain A, Simard G, Paoli F, Kulik W, Vaz FM,
Blasco H, Chantepie A, Labarthe F. Cosson L, Toutain
A, Simard G, Kulik W, Matyas G, Guichet A, Blasco H,
Maakaroun-Vermesse Z, Vaillant MC, Le Caignec C,
Chantepie A, Labarthe F. Barth syndrome in a female
patient. Mol Genet Metab. 2012 May;106(1):115-20. Epub
2012 Jan 24.
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.
Hanke SP, Gardner AB, Lombardi JP, Manning PB, Nelson
DP, Towbin JA, Jefferies JL, Lorts A. Left ventricular
noncompaction cardiomyopathy in Barth syndrome:
An example of an undulating cardiac phenotype
necessitating mechanical circulatory support as a bridge to
transplantation. Pediatr Cardiol. 2012 Dec;33(8):1430-4.
Epub 2012 Mar 17.
Wyatt (age 5).
Page 10
Page 11
2012 (cont’d)
Tafazzin deficiency in mouse model of Barth syndrome
leads to unique developmental cardiomyopathy
characterized by ventricular myocardial hypertrabeculationnoncompaction and early lethality. Central role of
cardiolipin and mitochondrial functioning strongly
implicated in cardiomyocyte differentiation and myocardial
patterning required for heart development.
Phoon CKL, Acehan D, Schlame M, Stokes DL, EdelmanNovemsky I, Yu D, Xu Y, Viswanathan N, Ren M.
Tafazzin knockdown in mice leads to a developmental
cardiomyopathy with early diastolic dysfunction preceding
myocardial noncompaction. J Am Heart Assoc. 2012
Apr;1(2). Epub 2012 Apr 24.*�
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.
Raches D, Mazzocco MM. Emergence and nature of
mathematical difficulties in young children with Barth
syndrome. J Dev Behav Pediatr. 2012 May;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.
Cade WT, Spencer CT, Reeds DN, Waggoner AD, O’Connor
R, Maisenbacher M, Crowley JR, Byrne BJ, Peterson LR.
Substrate metabolism during basal and hyperinsulinemic
conditions in adolescents and young-adults with Barth
syndrome. J Inherit Metab Dis. 2013 Jan;36(1):91-101.
Epub 2012 May 12.*�
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.
Reynolds S, Kreider CM, Bendixen R. A mixed-methods
investigation of sensory response patterns in Barth
syndrome: A clinical phenotype? Am J Med Genet Part A. 7 Jun 2012 Jul;158A(7):1647-53.*�
Page 12
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.
Ronvelia D, Greenwood J, Platt J, Hakim S, Zaragoza MV.
Intrafamilial variability for novel TAZ gene mutation: Barth
syndrome with dilated cardiomyopathy and heart failure in
an infant and left ventricular noncompaction in his greatuncle. Mol Genet Metab. 2012 Nov;107(3):428-32. Epub
2012 Sep 18.
Review article detailing longitudinal data collected,
including growth curves, from Barth Syndrome Registry and
Repository.
Roberts AE, Nixon C, Steward CG, Gauvreau K, Maisenbacher
M, Fletcher M, Geva J, Byrne BJ, Spencer CT. The Barth
Syndrome Registry: Distinguishing disease characteristics
and growth data from a longitudinal study. Am J Med
Genet A. 2012 Nov;158A(11):2726-32. Epub 2012 Oct 8.
(Open Access)*�
2013
Summary of clinically important information about Barth
syndrome.
Jefferies JL. Barth syndrome. Am J Med Genet C Semin Med
Genet. 2013 Aug;163(3):198-205. Epub 2013 Jul 10. (Open
Access)
(Photos courtesy BSF)
Highlights of Current Clinical Knowledge
“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
Page 13
Highlights of Current Clinical Knowledge
2013 (cont’d)
Review of recent advances in understanding molecular and
cellular bases of neutropenia in Barth syndrome.
Aprikyan AA, Khuchua Z. Advances in the understanding of
Barth syndrome. Br J Haematol. 2013 May;161(3):330-8.
Epub 2013 Feb 25. �
Our Mission is...
Saving lives through education, advances in treatment,
and finding a cure for Barth syndrome.
Report from French historical experiences with Barth
syndrome individuals and how good medical practices
contributed to survival.
Rigaud C, Lebre A, Touraine R, Beaupain B, Ottolenghi
C, Chabli A, Ansquer H, Ozsahin H, Di Filippo S, De
Lonlay P, Borm B, Rivier F, Vaillant M, Mathieu-Dramard
M, Goldenberg A, Viot G, Charron P, Rio M, Bonnet D,
Donadieu J. Natural history of Barth syndrome: A national
cohort study of 22 patients. Orphanet J Rare Dis. 2013 May
8;8:70. (Open Access) *�
Extended use of Berlin Heart EXCOR as bridge to transplant
in 3-year old Barth syndrome individual.
Dedieu N, Giardini A, Steward CG, Fenton M, Karimova
A, Hsia TY, Burch M. Successful mechanical circulatory
support for 251 days in a child with intermittent severe
neutropenia due to Barth syndrome. Pediatr Transplant.
2013 Mar;17(2):E46-9. Epub 2012 Nov 28. �
Clinical report from Italian population detailing six Barth
syndrome patients with five harboring new mutations in
the tafazzin gene including three deletions.
Ferri L, Donati MA, Funghini S, Malvagia S, Catarzi S, Lugli
L, Ragni L, Bertini E, Vaz FM, Cooper DN, Guerrini RR,
Morrone A. New clinical and molecular insights on Barth
syndrome. Orphanet J Rare Dis. 2013 Feb 14;8(1):27. doi:
10.1186/1750-1172-8-27. �
Comprehensive review article about Barth syndrome.
Clarke SLN, Bowron A, Gonzalez IL, Groves SJ, Newbury-Ecob
R, Clayton N, Martin RP, Tsai-Goodman B, Garratt V, Ashworth
M, Bowen VM, McCurdy KR, Damin MK, Spencer CT, Toth MJ,
Kelley RI, Steward CG. Barth syndrome. Orphanet Journal of
Rare Diseases 2013, 8:23. (Open Access) *�
“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
Page 14
Raphaël, age 4.
(Photo courtesy of Barth France ~ 2013)
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-Wieckowska A, Trubicka J, Werner B,
Kokoszynska K, Pajdowska M, Pronicki M, Czarnowska E,
Lebiedzinska M, Sykut-Cegielska J, Ziolkowska L, Jaron W,
Dobrzanska A, Ciara E, Wieckowski MR, Pronicka E. Left
ventricular noncompaction (LVNC) and low mitochondrial
membrane potential are specific for Barth syndrome. J
Inherit Metab Dis. 2013 Jan 30. [Epub ahead of print]
“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
Page 15
Barth Syndrome Foundation
Resources for Barth Syndrome Research
Resources for Healthcare Providers and Families
The Barth Syndrome Foundation (BSF) and its affiliates are a group
of international non-profit organizations that provide information,
resources and services for healthcare professionals and families
worldwide. Advising the group is a world-class Scientific and
Medical Advisory Board (SMAB), comprised of clinicians and
scientists who are leading experts in Barth syndrome.
BSF’s website (www.barthsyndrome.org) contains the most upto-date educational materials and research findings, including
a comprehensive on-line library which serves both the medical
community and affected families.
BSF’s International Barth Syndrome Conference, held every two
years, is really two simultaneous meetings. One meeting brings
together doctors and scientists involved in the many aspects of the
disorder to discuss the latest underlying scientific developments
and clinical insights; it is a unique experience that encourages
collaboration and accelerates advances in understanding and
treatment. The other is a family meeting in which the latest
information is discussed with families. Free consultation sessions
are also held enabling families to meet with medical experts from
around the world. In addition, opportunities to participate in
research studies and provide important clinical data and biological
samples to the Barth Syndrome Registry and Repository are
offered to Barth syndrome individuals.
The Sci/Med Listserv is an ongoing forum where members of our
international Scientific and Medical Advisory Board, clinicians and
researchers collaborate, ask questions and exchange the latest
information.
(Photo courtesy of Amanda Clark ~ 2012)
The Family Listserv is a forum where healthcare providers and
families engage in open discussions on the many aspects of
this disorder and its treatment. It is an immediate educational
resource for families.
Ned and Milosh (age 3).
Page 16
Research Grant Program
BSF and its affiliates sponsor a competitive research grant
program to facilitate advances in Barth syndrome understanding
and to encourage the discovery of new treatments. Grant
applications are evaluated by BSF’s international Scientific
and Medical Advisory Board, with input from expert outside
reviewers. Over the past eleven years, we have awarded
72 separate grants totaling almost US $2.7 Million, to 43
investigators around the world.
Barth Syndrome Registry & Repository
The Barth Syndrome Foundation (BSF) has been selected to
participate in a two-year pilot project of the National Institutes
of Health (NIH) called the Global Rare Disease Registry and
Data Repository (GRDR). As a pilot participant, BSF will work
in collaboration with leaders in rare disease research at
the Office of Rare Diseases Research, National Center for
Advancing Translational Sciences, National Institutes of Health,
PatientCrossroads, Children’s Hospital of Philadelphia, and
WebMD. The GRDR program will collect de-identified patient
health information from participating registries established by
individual rare disease organizations in order to allow analyses
of data across many rare diseases as well as to facilitate clinical
trials and other studies. This GRDR program builds on our existing
Registry & Repository and has been established to promote the
collection and sharing of clinical histories and biological samples
(including cell lines) of Barth syndrome patients. The Registry &
Repository are available to any qualified researcher, worldwide,
who is interested in studying Barth syndrome. For a direct link,
please visit the homepage of BSF’s website.
Human Tafazzin Gene Mutation & Variation Database
A central, up-to-date database listing all known mutations
and variations in the human tafazzin (TAZ or G4.5) gene was
established by and is maintained by BSF. This is a very valuable
resource which can be easily accessed through our main
website. We strongly encourage anyone who knows of a new
case (even if it involves a mutation or variation that is already
listed) to contact the list master for inclusion in this database.
For further information on our research programs, please visit
our website at www.barthsyndrome.org.
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
Page 17
Please Join Us
•Join BSF at no cost.
•Be kept up-to-date on the latest
educational materials and research
findings.
Aiden (age 2)
•Gain access to and participate in
informative listservs to collaborate
and share information.
•Receive an advance invitation to our
Bly (age 9)
Noah (age 11)
multi-track International Scientific,
Medical and Family Conference
held every two years (with the next
scheduled for late June 2014 in
Clearwater, Florida). Please visit BSF’s
website for additional information.
•Participate in the Barth Syndrome
Registry & Repository to further
research. For a direct link, please visit
the homepage of BSF’s website (www.
barthsyndrome.org).
R.J. (age 15)
•Receive our newsletter which delivers
relevant and timely research, medical,
and organizational information.
Please contact us for more
information.
Kevin (age 24)
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
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www.barthsyndrome.org
Barth Syndrome Foundation, Inc.
PO Box 618
Larchmont, New York 10538
Telephone: (850) 273-6947
Fascimile: (518) 213-4061
E-mail: bsfinfo@barthsyndrome.org
Website: www.barthsyndrome.org
Affiliates
Association Barth France
12, rue Lalo
75116 Paris
France
Telephone: +33 1 45 00 86 12
E-Mail: associationbarthfrance@orange.fr
Website: http://www.barthfrance.com
Barth Syndrome Trust (United Kingdom & Europe)
1 The Vikings
Romsey
Hampshire S051 5RG
United Kingdom
Telephone: +44(0)1794 518785
E-mail: info@barthsyndrome.org.uk
Website: www.barthsyndrome.org.uk
Barth Syndrome Foundation of Canada
162 Guelph Street
Suite 115
Georgetown, ON L7G 5X7
Canada
Telephone: (905) 873-2391
E-mail: inquiries@barthsyndrome.ca
Website: www.barthsyndrome.ca
Barth Trust of South Africa
49 Abelia Road
Kloof, Pinetown
3610 Natal
South Africa
Telephone: 082-465-1965
E-mail: jthorpe@barthsyndrome.org
Website: www.barthsyndrome.org/South_Africa.html
Page 19
Barth Syndrome Foundation
International Scientifc and Medical
Advisory Board
Michael Schlame, MD – Chairman
Cell Biology & Anesthesiology, New York University School of Medicine,
New York, New York
Peter G. Barth, MD, PhD – Emeritus
Pediatric Neurology (retired), Emma Children’s Hospital/Academic
Medical Center, Amsterdam, The Netherlands
W. Todd Cade, PT, PhD
Physical Therapy & Internal Medicine, Washington University School of
Medicine, St. Louis, Missouri
Gerald F. Cox, MD, PhD
Clinical Genetics, Children’s Hospital, Boston, Massachusetts;
Clinical Research, Genzyme Corp., Cambridge, Massachusetts
Iris L. Gonzalez, PhD
Molecular Diagnostics Lab (retired), A. I. duPont Hospital for Children,
Wilmington, Delaware
Miriam L. Greenberg, PhD
Biological Sciences, Wayne State University, Detroit, Michigan
Grant M. Hatch, PhD
Lipid Lipoprotein Research, University of Manitoba, Winnipeg, Canada
Richard I. Kelley, MD, PhD
Division of Metabolism, Kennedy Krieger Institute, Johns Hopkins
University, Baltimore, Maryland
William T. Pu, MD
Pediatric Cardiology, Boston Children’s Hospital; Harvard Stem Cell
Institute, Boston, Massachusetts
Mindong Ren, PhD
Cell Biology, New York University School, of Medicine, New York, New York
Colin G. Steward, PhD, FRCP, FRCPCH
Pediatric Hematology, Bristol Royal Hospital for Children, Bristol, England
Arnold Strauss, MD
Pediatrics and Research, Cincinnati Children’s Hospital Medical Center;
Cincinnati Children’s Research Foundation, Cincinnati, Ohio
Jeffrey A. Towbin, MD
Pediatric Cardiology, Cincinnati Children’s Hospital Medical Center &
University of Cincinnati, Cincinnati, Ohio
Ronald J. A. Wanders, PhD
Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands
Katherine R. McCurdy – ex-officio
Board Member, Barth Syndrome Foundation, Inc.
Matthew J. Toth, PhD – ex-officio
Science Director, Barth Syndrome Foundation, Inc.
Reviewed by SMAB Clinical Members
Healthcare Professional Brochure ~ October 2013
www.barthsyndrome.org
Page 20