Who first described Barth Syndrome?
Barth Syndrome is named after Dr. P.G. Barth who is affiliated with Emma Children's Hospital/University of Amsterdam Academic Medical Center in Amsterdam, Netherlands. He and his colleagues are credited with first describing the features of Barth Syndrome in 1981. The description of the phenotype (signs and symptoms) of Barth Syndrome was expanded by Dr. Richard I. Kelley at the Kennedy Krieger Institute in Baltimore, Maryland, who first described the excess excretion of certain organic acids in the urine of patients with Barth Syndrome. And the G4.5 gene was located and sequenced in 1996 by Silvia Bione et al. at the Institute of Genetics, Biochemistry and Evolution in Pavia, Italy.
How common is Barth Syndrome?
This disease is thought to be very rare. However, as is often the case with rare disorders, increased awareness of the disorder among medical practitioners and the public may lead to increased reports of its incidence. Since so little is known about Barth Syndrome at the biochemical and molecular level, it is possible that many cases go undetected. At present, there are known to be two families with affected family members in Australia, and a few dozen in the United States, Canada, and Europe. A recent paper from England found 5 new boys with Barth syndrome in one hospital in 7 years. They speculate that Barth is underdiagnosed and are conducting a frequency study (See Cantlay, et. al. J. Pediatr. 1999;135(3):311-315).
How is Barth Syndrome Inherited?
Barth Syndrome is inherited in an X-linked fashion, which means that a woman may carry an altered BTHS gene and not show symptoms of Barth Syndrome because she is "protected" by having a normal version of the gene on her second X chromosome. Males carrying the altered gene are likely to be affected. However, not every mother of an affected boy is a carrier for Barth Syndrome. Sometimes boys are affected because of a new mutation on their X chromosome. If a woman is a carrier, though, each son is at a 50% risk for being affected with Barth Syndrome, and each daughter has a 50% chance of being a carrier.
Why are there different names for the Barth Gene and Protein(s)?
Research investigators often give genes affectionate or in-house names. BTHS is the official genome name of the gene that when altered, causes Barth Syndrome. Another name that has been used is G4.5. The proteins are officially named Taffazins, but are also called BTHS and G4.5 proteins. We use BTHS to describe both the gene and protein products.
What do we know about the function of the BTHS gene?
The function of the BTHS gene is now known! Dr. Vreken's laboratory at the Academic Medical Center, University of Amsterdam, in the Netherlands has shown in yeast and in cultured fibroblasts that the defect is due to a defect in cardiolipin remodeling of the inner mitochondrial membrane. Cardiolipin deficient in linoliec acid is thought to be the missing final product (C18:2 is very reduced). Some of the techniques include Thin Layer chromatography (TLC), Tandem Mass-Spectroscopy, tritiated hydrogen incorporation, and radioactive fatty acid incorporation. Their work is now submitted to the journal Lancet, so keep you eyes peeled for this seminal article! I will post further details (they will have their own detailed page) after their paper becomes published.
Is there a treatment or cure for Barth Syndrome?
There is no cure, and few experts on treating Barth Syndrome. Physicians may be able to alleviate and control symptoms by administering drugs, altering diet, or performing surgery.
What can you tell me about the Barth gene?
The BTHS gene is 6,234 bases in length (this includes the 5' and 3' untranscribed regions). In human chromosomal DNA, the entire gene length is not transcribed and translated into proteins. When the BTHS gene is expressed, the DNA is "read" and transcribed into pre-messenger RNA (pre-mRNA). There are non-coding regions that are spliced out of the pre-mRNA strand, and other modifications are made to the pre-mRNA to convert it to messenger RNA (mRNA). The coding gene regions are called exons, and the non-coding regions are called introns. The longest possible coding mRNA of the BTHS gene is only 879 nucleotides long. There are 11 exons, and 10 introns (see the below diagram). The lines below the BTHS gene represent possible mRNA strands that can be transcribed. No one knows if some of, or all of these RNA strands are found in normal or Barth Syndrome cells. Once the mRNA is exported from the nucleus, it can be translated from mRNA into a polypeptide (in other words, a protein or an enzyme). A polypeptide is a series of chemically linked peptides (also known as amino acids). The longest possible amino acid sequence is 292 residues in length, and would weigh 33.5 kDa.
Last Updated 06/20/00 by the Metz Lab.