Barth Syndrome
Overview

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 Barth syndrome, 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.

Please see Barth Syndrome FAQs, Barth Syndrome Informational Sheets, Healthcare Professional Brochure, and our up-to-date bibliography for a wealth of information about Barth syndrome.

Inheritance

Barth syndrome (BTHS) is an X-linked genetic condition, usually transmitted from mother to son (although there is a relatively high incidence of new mutations in Barth syndrome and confirmed case reports of female Barth syndrome patients). A mother who is a carrier of a Barth syndrome mutation (the gene is named tafazzin — also called TAZ or G4.5) shows no signs or symptoms of this disorder herself, probably due to skewed X-chromosome inactivation.

There is a 50% chance that a boy born to a female carrier will have Barth syndrome; whereas, 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, no sons will be affected. Because there are proven non-carrier mothers, all mothers of Barth syndrome children should be tested in order to define the genetic risk in each family.

Any male child related through the female line to a Barth syndrome individual should be tested for the disorder, as there can be great variation in phenotype even among affected siblings.

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 (usually dilated with variable myocardial hypertrophy, sometimes with left ventricular noncompaction and/or endocardial fibroelastosis).

  • Neutropenia (Chronic, Cyclic, or 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.

  • Underdeveloped Skeletal Musculature and 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 BTHS.

  • 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 a growth pattern similar to but often more severe than constitutional growth delay with accelerated growth to normal height during mid- to late- teenage years.

  • Exercise Intolerance – Due to early fatigue.

  • Cardiolipin Abnormalities – A failure of BTHS mitochondria (the “powerhouses” or primary energy producers in cells) to make adequate amounts of tetralinoleoyl-cardiolipin, an essential lipid (fat-like molecule) for normal mitochondrial structure and energy.

  • 3-Methylglutaconic Aciduria, Type II (MGA, Type II) – (Typically a 5- to 20- fold 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.

Historically, individuals died of heart failure or infection by three years of age, but with improved diagnosis, appropriate medical treatment and monitoring of all symptoms, the survival rate and future of these individuals is much brighter.

Please remember this information is not intended to serve as medical advice and should not be used for diagnosing or treating a health problem or disease. It is not a substitute for professional care. If you suspect you or your children may have Barth syndrome you should consult your health care provider.

Resource Documents

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