Barth syndrome

Barth syndrome is an inborn error of phospholipid metabolism that primarily affects the heart and skeletal muscles, and is characterized by cardiomyopathy, neutropenia, growth delay, and organic aciduria. Mutations in the TAFAZZIN gene disrupt normal phospholipid remodeling, leading to the clinical manifestations seen in affected individuals. As an X-linked condition, it predominantly affects males, with female family members sometimes showing milder symptoms due to variable X-inactivation. This condition is rare, affecting approximately 1 to 9 per million people.

Individuals with Barth syndrome present with a range of multisystem features. Characteristic findings include cardiomyopathy (with both hypertrophic and dilated presentations), skeletal myopathy, and a reduced neutrophil count, which contribute to recurrent infections. Distinctive facial features such as a pointed chin, broad forehead, full cheeks, and macrotia are commonly observed, along with motor delay, exercise intolerance, fatigue, failure to thrive, and 3-methylglutaconic aciduria. Not all individuals experience every feature, and severity varies considerably.

Barth syndrome is caused by pathogenic variants in the TAFAZZIN gene, which plays a crucial role in phospholipid metabolism and the maintenance of mitochondrial function. The condition is inherited in an X-linked pattern, meaning that the mutation is typically passed from carrier females to their sons, while female relatives may experience milder symptoms due to skewed X-inactivation. Genetic counseling is recommended for families to understand the inheritance pattern, recurrence risks, and implications for family planning.

Currently, management of Barth syndrome focuses on supportive care and symptom management, with treatment tailored to the individual through a multidisciplinary approach. Regular surveillance is an essential part of long-term care, helping to identify potential complications—particularly related to cardiac function and infection risk—before they become more serious. Patients should discuss treatment options with their healthcare team to determine which therapies and monitoring strategies are most appropriate, and genetic counseling is recommended to support affected families.

Outcomes for individuals with Barth syndrome can vary widely depending on symptom severity, age at diagnosis, and access to specialized care. While some individuals experience a period of stabilization following the onset of symptoms, others may face later complications related to cardiac or muscular function. With current standards of care, many individuals live into adulthood and benefit from ongoing multidisciplinary management. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors for personalized guidance.

Clinical trials are underway exploring new treatment approaches for Barth syndrome. Several studies are currently investigating innovative therapies, and individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.