Barth syndrome
Encyclopedia
Barth syndrome also known as 3-Methylglutaconic aciduria type II, is a X-linked genetic disorder
.
(dilated or hypertrophic, possibly with left ventricular noncompaction and/or endocardial fibroelastosis), neutropenia (chronic, cyclic, or intermittent), underdeveloped skeletal musculature and muscle weakness, growth delay, exercise intolerance, cardiolipin abnormalities, and 3-methylglutaconic aciduria.
It can be associated with stillbirth
.
To date, Barth syndrome is found exclusively in males.
for his research and discovery in 1983. He described a pedigree chart
, showing that this is an inherited trait.
gene
(TAZ, also called G4.5) are closely associated with
Barth syndrome. The tafazzin gene product is believed to function as an acyltransferase in complex lipid metabolism. In 2008, Dr. Kulik found that all the BTHS individuals that he tested had abnormalities in their cardiolipin
molecules, a lipid found inside the mitochondria of cells. Cardiolipin is intimately connected with the electron transport chain
proteins and the membrane structure of the mitochondria which is the energy producing organelle of the cell. The human tafazzin gene, NG_009634, is listed as over 10,000 base pairs in length, and the full-length mRNA, NM_000116, is 1919 nucleotides long encoding 11 exons with a predicted protein length of 292 amino acids and a molecular weight of 33.5 kDa. The tafazzin gene is located at Xq28; the long arm of the X chromosome. Mutations in tafazzin that cause Barth syndrome span many different categories: missense, nonsense, deletion, frameshift, splicing (see Human Tafazzin (TAZ) Gene Mutation & Variation Database).
iPLA2-VIA has been suggested as a target for treatment.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
.
Presentation
Though not always present, the cardinal characteristics of this multi-system disorder include: cardiomyopathyCardiomyopathy
Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
(dilated or hypertrophic, possibly with left ventricular noncompaction and/or endocardial fibroelastosis), neutropenia (chronic, cyclic, or intermittent), underdeveloped skeletal musculature and muscle weakness, growth delay, exercise intolerance, cardiolipin abnormalities, and 3-methylglutaconic aciduria.
It can be associated with stillbirth
Stillbirth
A stillbirth occurs when a fetus has died in the uterus. The Australian definition specifies that fetal death is termed a stillbirth after 20 weeks gestation or the fetus weighs more than . Once the fetus has died the mother still has contractions and remains undelivered. The term is often used in...
.
Incidence
It has been documented in greater than 120 males to date (see Human Tafazzin (TAZ) Gene Mutation & Variation Database). It is believed to be severely under-diagnosed and may be estimated to occur in 1 out of approximately 300,000 births. Family members of the Barth Syndrome Foundation and its affiliates live in the US, Canada, the UK, Europe, Japan, South Africa, Kuwait, and Australia.To date, Barth syndrome is found exclusively in males.
History
The syndrome was named after Dr. Peter Barth (pediatric neurologist) in the NetherlandsNetherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
for his research and discovery in 1983. He described a pedigree chart
Pedigree chart
A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next, most commonly humans, show dogs, and race horses....
, showing that this is an inherited trait.
Cause
Mutations in the tafazzinTafazzin
Tafazzin is a protein that in humans is encoded by the TAZ gene. Tafazzin is highly expressed in cardiac and skeletal muscle. It is involved in the metabolism of cardiolipin....
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
(TAZ, also called G4.5) are closely associated with
Barth syndrome. The tafazzin gene product is believed to function as an acyltransferase in complex lipid metabolism. In 2008, Dr. Kulik found that all the BTHS individuals that he tested had abnormalities in their cardiolipin
Cardiolipin
Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. The only other place that cardiolipin can be found is in the membranes of most bacteria. The name ‘cardiolipin’ is derived from the fact that it was first...
molecules, a lipid found inside the mitochondria of cells. Cardiolipin is intimately connected with the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
proteins and the membrane structure of the mitochondria which is the energy producing organelle of the cell. The human tafazzin gene, NG_009634, is listed as over 10,000 base pairs in length, and the full-length mRNA, NM_000116, is 1919 nucleotides long encoding 11 exons with a predicted protein length of 292 amino acids and a molecular weight of 33.5 kDa. The tafazzin gene is located at Xq28; the long arm of the X chromosome. Mutations in tafazzin that cause Barth syndrome span many different categories: missense, nonsense, deletion, frameshift, splicing (see Human Tafazzin (TAZ) Gene Mutation & Variation Database).
iPLA2-VIA has been suggested as a target for treatment.
Barth Syndrome Foundation
The Barth Syndrome Foundation (BSF), together with its affiliates, are the only worldwide volunteer organizations dedicated to saving lives through education, advances in treatment, and finding a cure for Barth syndrome. The Barth Syndrome Foundation sponsors a competitive Research Grant Program and International Conferences for affected families, attending physicians, and scientists every two years.See also
- 3-Methylglutaconic aciduria3-methylglutaconic aciduria3-Methylglutaconic aciduria is used to describe at least five different disorders that impair the body's ability to make energy in the mitochondria. As a result of this impairment, 3-methylglutaconic acid and 3-methylglutaric acid build up and can be detected in the urine.3-Methylglutaconic acid...
- noncompaction cardiomyopathyNoncompaction cardiomyopathyNon-compaction cardiomyopathy , also called spongiform cardiomyopathy, is a rare congenital cardiomyopathy that affects both children and adults. It results from the failure of myocardial development during embryogenesis....
: mutations to the affected genes in Barth syndrome are also present here.
External links
- Barth Syndrome Foundation
- Human Tafazzin Gene Mutation & Variation Database
- Barth Syndrome Trust (United Kingdom & Europe)
- Barth Syndrome Foundation of Canada
- Barth Trust of South Africa
- Clinical Mass Spectrometry Laboratory - Kennedy Krieger Institute
- Barth Syndrome at National Organization for Rare Disorders (NORD)