Barth syndrome is a rare, genetic disorder that affects males. The condition is caused by mutations in the tafazzin gene, which codes for an enzyme involved in the synthesis of cardiolipin, an important lipid component of the inner mitochondrial membrane. The condition affects energy production in the mitochondria and leads to complications such as cardiomyopathy, muscle weakness and neutropenia.

Symptoms

Symptoms are not always present but some typical features of Barth syndrome include:

Cardiomyopathy - Cardiomyopathy describes a deterioration in the myocardium or heart muscle. The muscle is usually dilated or stretched with a varying degree of hypertrophy (increase in size).

Neutropenia - This refers to an abnormally low number of neutrophils (a type of white blood cell) in the blood.

Skeletal muscle development may be abnormal and muscle tone weak.

Levels of organic acids in the blood and urine may be increased. Levels of 3-methylglutaconic acid, for example, are typically raised by 5 to 20-fold.

Delayed growth during pre-teen years with growth often accelerated later on, in adolescence.

Cardiolipin abnormality

Complications of Barth's syndrome

Barth's syndrome may cause a range of complications some of which are listed below:

• Cardiomyopathy increases the likelihood of a dangerous abnormal heart rhythm or arrhythmia which can be fatal.
• Neutropenia increases the likelihood of infection, particularly of the mucous membranes such as the skin or inside of the mouth. A fever may also be present.
• Diarrhea and/or constipation.
• Weak muscle tone may lead to fatigue and difficulty exercising.
• Affected individuals may have feeding problems such as difficulty in sucking, swallowing or chewing, an aversion to some foods and be selective or fussy eaters.
• The risk of thrombosis or blood clots is increased.
• There is a risk of hypoglycemia or low blood sugar, especially when a child is newborn.
• Chronic (long-term) headache, abdominal pain, and/or body aches, particularly, during puberty.
• Mild learning disabilities may develop.
• The risk for osteoporosis is increased.

Phases of Barth syndrome

General phases of the disease are often but not always seen in children with the syndrome and these include:

1. Children often become seriously ill before the age of 5
2. Between ages 5 to 11, symptoms typically improve and patients tend to be free of symptoms
3. Adolescence often marks the return of symptoms

Treatment and management

There is no cure for Barth's syndrome and treatment is focused on managing the condition. Usually, the treatment approach to Barth's syndrome involves a team of specialists including experts in biochemistry, genetics and neurology as well as nurses, social workers, nutritionists and physical and occupational therapists.

Barth syndrome is suspected if a person presents with one of the main characteristics of the disease or if there is a family history of the condition. Diagnosis involves DNA sequencing to detect the tafazzin gene (TAZ, also called G4.5) mutation and analysis of cardiolipin in various cells and tissues.

Genetics

This is an X-linked inherited genetic disease, so a mother may be a carrier of the mutated gene despite not having any symptoms. There is a 50% chance that a boy born to a carrier mother will have the condition and a 50% chance that any daughters she has will be carriers themselves. All daughters of a male with the condition will be carriers but no sons will be affected.