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Kenneson et al. J Transl Genet Genom 2024;8:285-97 Journal of Translational
DOI: 10.20517/jtgg.2024.22
Genetics and Genomics

Original Article Open Access

The diagnostic odyssey, clinical burden, and natural
history of Barth syndrome: an analysis of patient

registry data

3
1
Aileen Kenneson , Yonglin Huang 2 , Erik Lontok , Lindsay Marjoram 2
1
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
Barth Syndrome Foundation, Larchmont, NY 10538, USA.
3
Coalition for Aligning Science, Chevy Chase, MD 20815, USA.
Correspondence to: Dr. Yonglin Huang, Barth Syndrome Foundation, 2005 Palmer Avenue #1033, Larchmont, NY 10538, USA.
E-mail: melissa.huang@barthsyndrome.org
How to cite this article: Kenneson A, Huang Y, Lontok E, Marjoram L. The diagnostic odyssey, clinical burden, and natural history
of Barth syndrome: an analysis of patient registry data. J Transl Genet Genom 2024;8:285-97. https://dx.doi.org/10.20517/jtgg.
2024.22

Received: 6 May 2024 First Decision: 18 Jul 2024 Revised: 26 Aug 2024 Accepted: 9 Sep 2024 Published: 24 Sep 2024
Academic Editor: Sanjay Gupta Copy Editor: Yu-Fei Wang Production Editor: Yu-Fei Wang

Abstract
Aim: Barth syndrome (BTHS; OMIM 302060) is an ultra-rare, complex, multi-system X-linked disorder that arises
from pathogenic mutations in the gene TAFAZZIN. BTHS is characterized by cardiomyopathy, skeletal myopathy,
muscle weakness, and neutropenia. To better understand the natural history and lived experience of affected
individuals, the Barth Syndrome Foundation maintains the patient-inputted Barth Syndrome Registry and
Repository (BRR).

Methods: Available cross-sectional and longitudinal participant data (n = 115) were analyzed to illustrate the
diagnostic odyssey, manifestations, and healthcare utilization across a broad range of affected individual age
groups.

Results: Individuals who experienced cardiomyopathy or heart failure as the first manifestation had the shortest
times to diagnosis compared to less appreciated manifestations (e.g., frequent infections, poor muscle tone,
growth delay). The most frequently reported manifestations across all ages were due to cardiac disorders (80.7%),
gastrointestinal (GI) disorders (68.7%), neutropenia or frequent infections (67.2%), and fatigue (60.9%), with
47.1% of participants scoring in the moderate-to-severe range of the Patient-Reported Outcomes Measurement
Information System (PROMIS) Fatigue Short Form 8A survey. Participants saw, on average, 3.6 specialists in the

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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