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Kenneson et al. J Transl Genet Genom 2024;8:285-97 https://dx.doi.org/10.20517/jtgg.2024.22 Page 287

[20]
nutritionists, physical therapists, occupational therapists, and psychologists .

Previously published natural history reports have thoroughly described the most commonly reported
of
aspects BTHS; however, other disease manifestations have been underappreciated and underexplored
In
[e.g., gastrointestinal (GI) issues, nutritional challenges, fatigue]. 2006, the Barth Syndrome Foundation
(BSF; https://barthsyndrome.org), patient advocacy group serving those affected with BTHS and their
a

families [21] , partnered with researchers and clinicians develop the BTHS Registry and Repository

to

a
to
(BRR) [22] . The BRR patient-reported and medically abstracted registry and was established further the
is
of
of
all
or
to
is
understanding the natural progression BTHS. Enrollment open living deceased individuals
of
by
affected BTHS worldwide. The objective this study was provide comprehensive overview the
a
to
of
its
disease across the lifespan and illustrate diagnostic odyssey and clinical burden. Moreover, advancements
an
in diagnosis and disease management have led increased number BTHS-affected individuals
to
of
to
a
surviving later into adulthood . We sought incorporate data from wider age range (i.e., infants
to
[23]
To
to
of
adults >50 years age) affected individuals help better understand disease progression over time.
of
of
better elucidate the natural history and lived experience BTHS, we used patient- and/or caregiver-
to
reported cross-sectional and longitudinal data from the BRR gather detailed information on the
on
prevalence BTHS signs and manifestations age group, the diagnostic timeline based presentation,
by
of
and healthcare utilization.
METHODS
Barth syndrome registry and repository
by
The Barth Syndrome Registry and Repository (BRR) , which maintained the BSF, stores detailed
i
s
[22]
i
n
information about individuals diagnosed with BTHS, and was developed conjunction with clinicians with
BTHS.
expertise in the disease. The BRR acts as a amass data about the natural history of
platform to
their
the
age
Individuals diagnosed with BTHS or caregivers (if affected individual is years of or
under 18
enrolling at
unable to provide consent) can participate by the BRR website (http://barthsyndromeregistry
.org). After providing consent or assent to participate,

participants are asked to complete several surveys that focus on basic demographic information,
med ical history, heart transplant status, quality of life (fatigue),and other clinical information.

Participants the clinical, heart transplant, and quality of life surveys annually.

are requested to complete

The self- and/or caregiver-reported data are entered into a secure password-protected, web-

based database via the Invitae Patient Insights Network. Institutional Review Board approval of the BRR was
obtained from North Star Review Board (IRB #: NB300158).
Participants

Only registry participants with a confirmed genetic test or clinical diagnosis of BTHS were included in this

analysis (n = 115). The study population was categorized as probands (n = 90) or other family members.

Non-probands (n = 10) were defined as participants who had a relative in the BRR diagnosed at an earlier

time, as well as those who reported being diagnosed before manifestations appeared due to an affected

relative. For the analysis of manifestations by age, all participants, both living and deceased, were included.

However, for the analysis of medication usage by age and the analysis of specialist medical care, only living

participants were included. Each individual was included once per age group, and was classified as having
the clinical phenotype if they reported having it at any time period within that age group.
Medical history and clinical information
Medical history and clinical information were obtained via self- or caregiver report via a clinical survey. The
questions covered the age at which the diagnosis was made, whether there was any family history of BTHS,
what specialists the participant visited throughout a 12-month period and the frequency, their clinical
manifestations and medications, transplantation status, and significant medical events. Individuals were