Barth Syndrome and Referral to Heart Transplantation: Single-Center Experience and Literature Review

Barth syndrome is an X-linked mitochondrial disorder caused by pathogenic variants in the TAZ gene, resulting in impaired cardiolipin remodeling and mitochondrial dysfunction. Cardiomyopathy is the most prominent manifestation, often presenting in early infancy and potentially progressing to advanced heart failure requiring heart transplantation. Due to phenotypic overlapping with other cardiac diseases, diagnosis is frequently delayed. The aim of this study was to describe our experience with pediatric patients with Barth syndrome referred to heart transplantation and their clinical outcomes at the largest heart transplantation center in Latin America.

We retrospectively reviewed pediatric patients with Barth syndrome referred for heart transplantation evaluation at the Heart Institute (InCor), University of São Paulo Medical School, between 1992 and 2025. Clinical characteristics, heart failure severity, transplant evaluation, treatment response, listing status, and outcomes were described.

We retrospectively reviewed three pediatric patients with genetically confirmed Barth syndrome referred to our center for heart transplantation evaluation. Despite severe early cardiac involvement, they exhibited markedly different heart failure trajectories. Barth syndrome cardiomyopathy follows a highly heterogeneous clinical course. Although some patients demonstrate significant recovery with optimized heart failure therapy, others progress to end-stage heart failure requiring transplantation. Our experience reinforces that early referral to pediatric heart transplant centers and individualized transplant listing based on longitudinal clinical evolution, rather than left ventricular ejection fraction alone, may optimize patient outcomes.

Early referral to pediatric heart transplant centers and individualized transplant listing based on longitudinal clinical evolution may optimize outcomes in Barth syndrome.