Barth syndrome is a rare genetic disorder that primarily affects males, impacting several bodily systems. It is characterized by specific abnormalities in heart function and muscle strength.
Defining Barth Syndrome
Barth syndrome is a rare, X-linked genetic disorder, meaning it is passed down through families on the X chromosome and predominantly affects males. It is characterized by distinct features, most notably a weakened and enlarged heart, known as dilated cardiomyopathy. This condition impairs the heart’s ability to pump blood effectively throughout the body.
Another defining characteristic is skeletal myopathy, which refers to weakness in the voluntary muscles of the body. Individuals often experience low levels of neutrophils, a type of white blood cell, a condition called neutropenia, which can increase susceptibility to infections. A delay in growth and the presence of 3-methylglutaconic acid in the urine are also classic indicators of Barth syndrome. The severity and combination of symptoms can vary among individuals.
Genetic Cause and Inheritance
Barth syndrome arises from a mutation in the TAZ gene. This gene provides instructions for making a protein involved in cardiolipin synthesis, a lipid found predominantly in the inner membrane of mitochondria, the cell’s “powerhouses” that generate chemical energy. A defect in the TAZ gene leads to abnormal cardiolipin, which impairs mitochondrial function and contributes to the wide range of symptoms seen in Barth syndrome.
The condition follows an X-linked recessive inheritance pattern. Males, who have only one X chromosome, are primarily affected if they inherit the mutated gene. Females typically carry two X chromosomes, so if one X chromosome carries the mutation, the other usually compensates, making them carriers who are often asymptomatic or experience milder symptoms. Genetic counseling is an important consideration for affected families.
Key Symptoms and Manifestations
Dilated cardiomyopathy, where the heart muscle becomes thin and stretched, is a prominent feature. This can lead to symptoms like shortness of breath and fatigue, and can also increase the risk of heart failure and abnormal heart rhythms, known as arrhythmias.
Skeletal myopathy results in muscle weakness, which can manifest as difficulty with physical activities, delayed motor development in children, and persistent fatigue. The recurring neutropenia significantly elevates the risk of bacterial infections. Many individuals also experience a delay in growth, often resulting in shorter stature and delayed puberty. While 3-methylglutaconic aciduria is a metabolic marker used in diagnosis, it does not typically cause specific outward symptoms. Other potential manifestations include feeding difficulties in infants and overall exercise intolerance.
Diagnosis and Treatment Approaches
Diagnosis often begins with clinical suspicion based on characteristic symptoms. Laboratory tests include urine analysis for elevated 3-methylglutaconic acid and blood tests for neutropenia and cardiac biomarkers. Cardiac imaging, such as an echocardiogram, provides detailed views of the heart’s structure and function, helping to identify cardiomyopathy.
Confirmation is achieved through genetic testing, which identifies mutations in the TAZ gene. Analyzing mitochondrial cardiolipin content in fibroblast cells can also provide diagnostic evidence. While there is no cure, treatment focuses on managing symptoms to improve quality of life. Cardiac management involves medications like ACE inhibitors and beta-blockers. For severe neutropenia, granulocyte colony-stimulating factor (G-CSF) may be administered. Nutritional support addresses growth delays, and physical and occupational therapy manage muscle weakness.
Living with Barth Syndrome
Advancements in medical care have positively influenced the long-term outlook for individuals with Barth syndrome. Improved management strategies have led to better health outcomes and increased life expectancy. This progress underscores the importance of ongoing medical attention and specialized care.
Individuals benefit from a multidisciplinary care team, including cardiologists, geneticists, immunologists, nutritionists, and physical therapists. Patient advocacy groups provide support and resources. Research efforts continue to further understand the condition and develop targeted therapies.