Overview of Barth Syndrome

When you or your loved one is first diagnosed with Barth syndrome (BTHS), you can feel overwhelmed. You may not even have heard of Barth syndrome until now.  Learning all you can is a major step toward taking charge of your illness -- and your life.

These pages are intended to help you understand more about the diagnosis and treatment of Barth syndrome, and its impact on the day-to-day lives of  patients and their families. The better informed you are about BTHS, the more equipped you'll be to participate as an active member of your healthcare team.

Barth syndrome (BTHS; OMIM #302060) is a serious X-linked genetic disorder, primarily affecting males. It is caused by a mutation in the tafazzin gene (TAZ, also called G4.5), resulting in an inborn error of lipid metabolism.

Inheritance
Barth syndrome is an X-linked recessive genetic condition, generally transferred from mother to son. A mother who is a carrier of Barth syndrome shows no signs or symptoms of the disorder herself.

There is a 50% chance that a boy born to a female carrier will have Barth syndrome, while girls born to a carrier have a 50% risk of being carriers themselves. All daughters of a male with Barth syndrome will be carriers; however, none of his sons will be affected. There are several known non-carrier mothers, and for this reason we believe mothers should be tested.

(Follow link to view What's in Your Genes presentation)

Though not always present, cardinal characteristics of this multi-system disorder often include combinations and varying degrees of:

Cardiomyopathy
A weak heart muscle usually associated with enlargement of the heart (dilated or hypertrophic, possibly with left ventricular noncompaction and/or endocardial
fibroelastosis).

Neutropenia
(Chronic, Cyclic, Intermittent)
A reduction in “neutrophils”, a type of white blood cell that is most important for fighting bacterial infections. Neutropenia may predispose an individual to mouth ulcers, fevers and bacterial infections such as bacterial pneumonia and skin abscesses.

Muscle Weakness
All muscles, including the heart, have a cellular deficiency which limits their ability to produce energy. Muscle weakness and increased exertional fatigue are characteristic findings in Barth syndrome.

Growth Delay
During childhood most affected individuals are below-average in height and weight. This is often assumed to be evidence of poor nutrition or other secondary effects of a chronic illness, but that is rarely the case. In fact, some of the common nutritional treatments are contra-indicated. Through BSF´s registry, we have observed accelerated growth to normal height during mid- to late- teenage years.

3-Methylglutaconic Aciduria, Type II (MGA, Type II)
(An increase in an organic acid that can be measured in urine)
A result of abnormal mitochondria (the “powerhouses” or primary energy producers in cells) function. However, there have been reports of normal levels of 3-methylglutaconic acid (3MGA) in confirmed cases of Barth syndrome.

Cardiolipin Deficiency 
A failure of Barth syndrome mitochondria to make adequate amounts of tetralinoleoyl-cardiolipin, an essential lipid (fat-like molecule) for normal mitochondrial structure and energy.

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