Barth syndrome 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.

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.

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.

Barth syndrome is a rare, sex-linked genetic disorder of lipid metabolism that affects males. Typically, boys with Barth syndrome present with hypotonia (low muscle tone) and dilated cardiomyopathy (labored breathing, poor appetite, and/or slow weight gain) at or within the first few months after birth.

Other important features of Barth syndrome include bacterial infections because of neutropenia (a reduction in the number of white blood cells called neutrophils), muscle weakness, fatigue, and short stature. Although most children with Barth syndrome manifest all of these characteristics, some have only one or two of these abnormalities and, as a result, often are given incorrect diagnoses.

Barth syndrome occurs in many different ethnic groups and does not appear to be more common in any one group. To date, there are no good studies of the population or birth incidence of Barth syndrome; however probably fewer than 10 new Barth infants are identified each year in the United States, which suggests an incidence of only 1 in every 300,000 – 400,000 births.

The gene for Barth syndrome, Tafazzin (TAZ), is located on the long arm of the X chromosome (Xq28). Mutations in the TAZ gene lead to decreased production of an enzyme required for the synthesis of “cardiolipin,” a special lipid that is important in energy metabolism.

There is no specific treatment for Barth syndrome, but each of the individual problems can be successfully controlled, and both the heart disease and short stature often resolve entirely after puberty.

Source: Barth Syndrome Foundation