Biomarker and Genetic Testing Facilities for Barth Syndrome

Testing for Barth syndrome in the past has so far mostly been restricted to males with dilated cardiomyopathy (DCM) AND neutropenia AND excessive amounts of 3-methylglutaconic acid in their urine.

However, it is increasingly clear that the disease can behave very differently between affected males and in rare instances affect females.  Not all who are diagnosed with Barth syndrome will have low blood neutrophil counts.

While many individuals with Barth syndrome show a five to 20-fold increased level of 3-MGCA on quantitative analysis of urinary organic acids and BTHS is therefore also known as ‘type II 3-methylglutaconic aciduria’. 3-methylglutaric acid and 2-ethyl-hydracrylic acid levels are also increased.  

However, cases have been reported where urinary 3-MGCA levels have been normal in patients with TAZ mutations and levels may vary considerably even within a 24 hour period. 3-MGCA is also elevated in a collection of disorders of widely varying phenotype, with increasing opinion of making this a test as having poor diagnostic specificity.

Genetic Testing Registry

The Genetic Testing Registry  (GTR®) provides a central location for voluntary submission of genetic test information by providers. The scope includes the test's purpose, methodology, validity, evidence of the test's usefulness, and laboratory contacts and credentials. The overarching goal of the GTR is to advance the public health and research into the genetic basis of health and disease.

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Search Tips

1. Type "Barth syndrome" (with quotation marks) in the "Conditions/Phenotypes" search box, then press the search button
2. Click on the Testing link associated with Barth syndrome [3-Methylglutaconic Aciduria Type II]
3. You can select one or all laboratories to learn more about methods and details of each laboratory

Metabolites (Cardiolipin Testing)

Cardiolipin testing provides a practical approach to testing.  It can be performed very reliably on only a small volume of blood. The test result is usually available within one to two weeks through the Laboratory of Genetic Metabolic Diseases (LGMD) University Medical Center, Amsterdam.  It is a very good diagnostic marker for Barth syndrome.  Gene testing should still be performed as further confirmation in someone with a positive cardiolipin test. 

The Barth Service in Bristol, England recommends routine cardiolipin testing in all young males with dilated cardiomyopathy (DCM).  They further recommend cardiolipin testing in male babies/boys with left ventricular noncompaction (LVNC), unexplained neutropenia (especially with poor growth, developmental delay or weak muscles and easy fatigue) and in families with a male pattern of hypertrophic cardiomyopathy (HCM) but where no genetic cause can be found and other features suggestive of Barth syndrome are present.

Tips 

• Scroll down on to the cardiolipin section of the metabolites page of the LGMD website
• Click the cardiolipin tab
• Submission instructions and costs are provided in that section

Benefits of an Accurate Diagnosis:

• Saves lives and improves quality of life.
• Provides families and healthcare providers with an appreciation of the complexities and health risks of all components of the disorder, thereby yielding better outcomes for the affected individual.
• Provides families and healthcare providers an opportunity to access to data pertaining specifically to Barth syndrome.
• Provides families the opportunity for family planning.
• Provides families and educators the opportunity to develop individualized educational planning.
• Provides families and healthcare providers the opportunity to an informed approach to care, significantly reducing contra-indicated treatment risks.