This webpage was created as an assignment for Genetics 564, an undergraduate capstone course at the University of Wisconsin-Madison.
Barth Syndrome (BTHS)
Barth Syndrome (BTHS) is a rare and serious X-linked genetic disorder that affects mainly males. It is estimated to affect about 1 in 300,000 births worldwide, but this number may be higher due to under-diagnosis (1). The hallmark symptoms of Barth Syndrome are a large and weakened heart (dilated cardiomyopathy), weakened muscle (skeletal myopathy), low numbers of neutrophils (neutropenia), but is also known to present itself in many other heart and energy-related conditions (2,3).
Living with Barth Syndrome
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Symptoms of Barth Syndrome
The primary symptoms associated with Barth Syndrome are:
Other symptoms include:
- Low general skeletal muscle mass and weakness
- Feeding issues (difficulty sucking, swallowing, chewing)
- Cardiolipin (CL) abnormalities
- A general increase in the amount of acid (3-methylglutaconic aciduria) in the urine
How is Barth Syndrome diagnosed?
Barth Syndrome is a complex disease that manifests in a variety of symptoms. Often times, these symptoms are the first recognition that something could be wrong. Here are several common tests clinicians may order and what they might mean for you:
Genetic TestingTo know for certain if an individual does have Barth Syndrome, Genetic Testing for the disease is a must. Because Barth Syndrome is caused by mutations in the Tafazzin (TAZ) gene, a DNA sequence analysis for these mutations is a must for an accurate diagnosis.
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Urinalysis for 3-methylglutaconic aciduria (3-MGCA)
A build-up of excessive amounts of 3-MGCA in the urine can be a good indicator for Barth Syndrome, which is also known by the name Type II 3-methylglutaconic aciduria.
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Echocardiogram/CT Scan
Echocardiograms and cardiac CT scans can be an effective way to determine heart function and diagnose cardiomyopthies, such as a dilated cardiomyopathy. However, this may not clinically manifest until after the first six months of life.
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Complete Blood Count (CBC) Panel
Absolute Neutrophil Counts (ANC) often provide readings that may appear normal, even with neutropenia. Serial blood testing, either through multiple ANCs or CBCs (or a combination of both) could provide insight into whether or not a diagnosis of neutropenia is correct.
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Metabolite/Cardiolipin Testing
Despite the knowledge that cardiolipin function plays a role in Barth Syndrome, few labs have the clinical capability to test for cardiolipin (CL) levels. The Laboratory of Genetic Metabolic Diseases (LGMD) in Amsterdam has thorough instructions for ordering a test.
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How is Barth Syndrome inherited?
Barth Syndrome is a rare genetic disorder, involving the X-linked recessive inheritance of the TAFAZZIN gene, only affecting around 200 males in the world; however, this number may be higher (1). Because males have a single copy of the X chromosome, they are at higher risk for developing Barth Syndrome. Females are less likely to develop the disease, but can often act as carriers who my pass the disease on to offspring.
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What treatments are available?
Barth Syndrome does not have a cure, however many treatment options exist that focus on managing an individual's symptoms and taking preventative measures against complications.
Gaps in Knowledge
While significant progress has been made in understanding Barth Syndrome, there are still aspects of the disorder that remain unknown. It is known that mutations in the Tafazzin (TAZ) gene affect cardiolipin production and remodelling; however, the exact mechanisms by which these changes in cardiolipin composition lead to the specific symptoms of Barth Syndrome are not well understood. It is also uncertain whether Tafazzin (TAZ) mutations impact other cellular processes, which could be a contributing factor to the broad range of symptoms observed in the disorder.
Gene and Protein Function
Organizations Involved with Barth Syndrome
References:
Pictures used are hyperlinked to source.
- Clarke, et al. Barth syndrome. Orphanet J Rare Dis. 2013 Feb 12;8:23. doi: 10.1186/1750-1172-8-23.
- Barth, et al. An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci. 1983 Dec;62(1-3):327-55. doi: 10.1016/0022-510x(83)90209-5.
- Christodoulou, et al. Barth syndrome: clinical observations and genetic linkage studies. Am J Med Genet. 1994 Apr 15;50(3):255-64. doi: 10.1002/ajmg.1320500309.
- Garlid, et al. TAZ encodes tafazzin, a transacylase essential for cardiolipin formation and central to the etiology of Barth syndrome. Gene. 2020 Feb 5;726:144148. doi: 10.1016/j.gene.2019.144148.
- Thompson, et al. New targets for monitoring and therapy in Barth syndrome. Genetics in Medicine. 2016 Oct 16; 18(10). dio: 10.1038/gim.2015.204
- Ye, et al. Deletion of the Cardiolipin-specific Phospholipase Cld1 Rescues Growth and Life Span Defects in the Tafazzin Mutant: IMPLICATIONS FOR BARTH SYNDROME. Journal of Biological Chemistry. 2014 Feb 7; 289(6). doi: 10.1074/jbc.M113.529487
- Petit, et al. Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome. Cells. 2020 Oct 21;9(10):2333. doi: 10.3390/cells9102333.
- https://www.childrenshospital.org/conditions/barth-syndrome
- https://www.barthsyndrome.org/barthsyndrome/
- https://my.clevelandclinic.org/health/diseases/23219-barth-syndrome
Pictures used are hyperlinked to source.
Recent Visitors
Jeffrey Pietroske
University of Wisconsin-Madison
[email protected]
[email protected]
Last Updated: 5/09/2023
University of Wisconsin-Madison
[email protected]
[email protected]
Last Updated: 5/09/2023