Barth syndrome: mechanisms and management

Area of Science:

• Genetics and rare diseases
• Mitochondrial disorders
• X-linked recessive inheritance

Background:

• Barth syndrome is an ultra-rare, infantile-onset, X-linked recessive mitochondrial disorder.
• It is caused by variants in the TAZ gene, encoding cardiolipin transacylase tafazzin.
• Primarily affects males, presenting a significant diagnostic and therapeutic challenge.

Purpose of the Study:

• To review and synthesize current knowledge on Barth syndrome.
• Covering etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and outcomes.
• Providing a comprehensive overview for researchers and clinicians.

Main Methods:

• A comprehensive literature review was conducted.
• Utilizing MEDLINE database for relevant studies.
• Focusing on recent and earlier findings related to Barth syndrome.

Main Results:

• Phenotype is variable, commonly including cardiomyopathy, fibroelastosis, neutropenia, and mitochondrial myopathy.
• Biochemical markers like elevated 3-methylglutaconic acid and decreased cardiolipin are characteristic.
• Diagnosis confirmed by identifying causative TAZ variants; treatment is symptomatic.

Conclusions:

• Barth syndrome remains an orphan disease with fewer than 200 reported cases.
• Extensive research is underway for pathomechanisms and novel therapeutic strategies.
• Experimental approaches suggest potential for future causative treatments.