Information About Barth Syndrome | Endocrinology

Barth syndrome

What is Barth syndrome?

Barth syndrome is a metabolic disorder that affects the heart, muscles, immune system, and growth. It almost always occurs in children.

This typically appears during infancy or early childhood, but the age of onset can vary greatly.

Children with this disorder can develop serious heart problems, such as congestive heart failure, weakness of the heart muscle (cardiomyopathy), and serious arrhythmias. They may also have infection or sepsis.

Barth syndrome affects approximately 1 in 300,000 to 400,000 babies born worldwide.

Causes of Barth syndrome

Mutations in the TAZ gene cause Barth syndrome. The TAZ gene delivers instructions for making a protein called tafazzin. Tafazzin is found in structures called mitochondria, which are the energy production centers of cells. Tafazzin is involved in the alteration of a fat (lipid) called cardiolipin, which performs critical functions in the inner mitochondrial membrane. Once altered by tafazzin, cardiolipin is key to maintaining mitochondrial shape, energy production, and protein transport within cells.

Mutations in the TAZ gene result in the production of tafazzin proteins with little or no function. As a result, tafazzin cannot alter cardiolipin. Lack of functional cardiolipin disrupts normal mitochondrial shape and functions. Tissues with high energy demands, such as the heart and skeletal muscles, are more susceptible to cell death due to reduced energy production in the mitochondria.

Also, abnormally shaped mitochondria are found in pretentious white blood cells, which could affect their ability to grow (proliferate) and mature (distinguish), leading to neutropenia. Dysfunctional mitochondria probable lead to other signs and symptoms of Barth syndrome.

Symptoms of Barth syndrome

Symptoms associated with Barth syndrome can be apparent from birth, infancy, or early childhood. In rare cases, the disorder may not be diagnosed until adulthood. Most people with Barth syndrome have weakened heart muscle (cardiomyopathy) that leads to enlargement of the lower chambers of the heart (ventricles). Known as dilated cardiomyopathy, the signs of this condition are often present at birth or may appear during the first few months of life.

Dilated endocardial myopathy normally weakens the pumping action of the heart, reducing the volume of blood that circulates to the lungs and the rest of the body (heart failure). Symptoms of heart failure can depend on the child’s age and other factors. In young children, for example, heart failure can manifest as fatigue and shortness of breath on exertion.

Barth syndrome is also related with abnormally reduced muscle tone (hypotonia) and muscle weakness (skeletal myopathy), often leading to delays in the development of gross motor skills. Gross motor skills include activities such as crawling, walking, running, jumping, and balancing.

The weakness of the facial muscles can cause unusual facial expressions. Also, affected infants and children may not develop and may not gain weight at the expected rate. Some affected children have mild learning difficulties (although they usually have normal intelligence) and, in many cases, may be prone to recurrent bacterial infections due to low levels of circulating neutrophils in the blood (neutropenia).

In addition to the signs and symptoms stated above, people with Barth syndrome have abnormally high levels of a substance called 3-methylglutaconic acid in their urine and blood. Though, there does not appear to be an association between increased acid levels and the severity of other symptoms and signs associated with Barth syndrome.

This table lists the symptoms that people with this disease may have. For most diseases, symptoms vary from person to person. People with the same disease may not have all of the listed symptoms. This information originates from a database called Human Phenotype Ontology (HPO). The HPO collects information about symptoms that have been labelled in medical resources. The HPO is periodically updated. Use the HPO ID to admission more detailed information about a symptom.

Diagnosis of Barth syndrome

Barth syndrome is usually diagnosed during infancy or early childhood, but is diagnosed later in some patients. Diagnosis is based on clinical evaluation, identification of characteristic physical findings, a complete patient and family history, and a variety of specialized tests.

Consider Barth syndrome if someone has:

  • Cardiac findings such as dilated cardiomyopathy, hypertrophic cardiomyopathy, and non-compaction of the left ventricle
  • Elevated levels of 3-methylglutaconic acid in blood and / or urine
  • Neutropenia
  • Hypotonia
  • Growth retardation
  • Characteristic facial features

Manifold pregnancy losses involving a male fetus have been observed in some families with Barth syndrome.

Molecular genetic testing for mutations in the TAZ gene settles the diagnosis of Barth syndrome. The TAZ gene test can be done individually or as part of a multigene panel.

Clinical trials and studies

As part of routine monitoring, children’s growth and height are monitored regularly. Annual cardiac monitoring by ECG, echocardiogram and Holter monitor is considered.

Treatment for Barth syndrome

There is no specific treatment for Barth syndrome. Bacterial infections caused by neutropenia can be efficiently treated with antibiotics. The drug granulocyte colony stimulating factor, or GCSF, can stimulate the production of white blood cells in the bone marrow and help fight infection. Medications may be prescribed to control heart problems. The dietary extra carnitine has helped some children with Barth syndrome, but in others it has caused increased muscle weakness and even precipitated heart failure. Only careful dietary monitoring led by a physician or nutritionist familiar with the disorder can ensure adequate calorie and nutrient intake.

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