Barth syndrome

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Barth syndrome
Synonyms	3-Methylglutaconic aciduria type II, X-linked cardioskeletal myopathy and neutropenia
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Specialty	Genetics, Cardiology
Symptoms	Cardiomyopathy, neutropenia, muscle weakness, growth delay
Complications	N/A
Onset	Infancy
Duration	Lifelong
Types	N/A
Causes	Mutations in the TAZ gene
Risks	Family history
Diagnosis	Genetic testing, blood tests
Differential diagnosis	Dilated cardiomyopathy, mitochondrial disorders
Prevention	N/A
Treatment	Supportive care, heart transplantation
Medication
Prognosis	Variable, can be life-threatening
Frequency	Rare, estimated 1 in 300,000 to 400,000 live births
Deaths

Not to be confused with Bart syndrome.

Barth Syndrome
Synonyms	3-Methylglutaconic aciduria type II, X-linked cardioskeletal myopathy and neutropenia, BTHS, Cardioskeletal myopathy with neutropenia and abnormal mitochondria, Cardioskeletal myopathy-neutropenia syndrome
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Field	Medical genetics, Pediatrics, Cardiology
Symptoms	Dilated cardiomyopathy, Neutropenia, Short stature, Muscle weakness
Complications	N/A
Onset	Infancy
Duration	Lifelong
Types
Causes	TAZ gene mutation (X-linked recessive)
Risks
Diagnosis	Genetic testing, Echocardiogram, Blood test
Differential diagnosis	Other mitochondrial diseases, Primary immunodeficiency
Prevention	None
Treatment	Symptomatic management
Medication	Antibiotics, Heart failure medications
Prognosis	Variable; reduced life expectancy possible
Frequency	1–9 per 1,000,000
Deaths

Neutropenia is a key feature of Barth syndrome.

Barth syndrome is a rare genetic disorder that primarily affects males. It is characterized by a combination of symptoms including cardiomyopathy, neutropenia, skeletal muscle weakness, growth delay, and abnormal mitochondrial function. The condition is caused by mutations in the TAZ gene, which is located on the X chromosome and affects the metabolism of cardiolipin, a key phospholipid in mitochondrial membranes.

Genetics

Barth syndrome is inherited in an X-linked recessive pattern. Since males have only one X chromosome, a single mutation in the TAZ gene is sufficient to cause the disorder. Females can be carriers and may show mild symptoms due to lyonization (random X-inactivation). The TAZ gene encodes the enzyme tafazzin, which plays a crucial role in the remodeling of cardiolipin. Cardiolipin is an essential component of inner mitochondrial membranes, and its proper structure is vital for mitochondrial energy production. Mutations in TAZ lead to dysfunctional cardiolipin and mitochondrial impairment.

Clinical Features

Cardiomyopathy

The most serious manifestation is dilated cardiomyopathy, in which the heart becomes enlarged and weak, often leading to heart failure. Some patients may also have endocardial fibroelastosis, a thickening of the inner heart wall.

Neutropenia

Neutropenia, or a low count of neutrophils, increases the risk of bacterial infections. The degree of neutropenia can fluctuate and may be severe in some individuals.

Muscle Weakness and Fatigue

Affected individuals often experience muscle hypotonia and exercise intolerance due to mitochondrial energy deficiency.

Growth Delay

Short stature and delayed puberty are common features. These may result from nutritional deficiencies, chronic illness, or metabolic dysfunction.

Diagnosis

Diagnosis involves a combination of clinical evaluation, family history, and diagnostic testing:

• Genetic testing to identify mutations in the TAZ gene
• Blood tests showing neutropenia or elevated 3-methylglutaconic acid
• Echocardiography to detect cardiomyopathy
• Muscle biopsy or mitochondrial function tests in selected cases

Management

There is no cure for Barth syndrome. Treatment is supportive and includes:

• Medications for heart failure, including beta-blockers, ACE inhibitors, and diuretics
• Antibiotic prophylaxis or treatment for infections
• Granulocyte colony-stimulating factor (G-CSF) for severe neutropenia
• Nutritional support and growth monitoring
• Physical therapy to improve strength and mobility

Multidisciplinary care from cardiologists, geneticists, immunologists, and nutritionists is essential.

Prognosis

The prognosis varies depending on the severity of cardiac and hematological complications. With early detection and appropriate management, many individuals survive into adulthood, although some may experience reduced life expectancy due to heart failure or infections.

See also

• Genetic disorders
• Cardiomyopathy
• Mitochondrial diseases
• Neutropenia
• Tafazzin
• X-linked recessive inheritance

External links

• NIH Rare Diseases Information: Barth Syndrome
• Barth Syndrome Foundation

NIH genetic and rare disease info

• NIH info on Barth syndrome

Barth syndrome is a rare disease.