Testing
Barth syndrome is caused by mutations in the tafazzin (TAZ) gene
which is located on the X chromosome. TAZencodes a phospholipid
transacylase that promotes cardiolipin acyl chain remodeling.
Cardiolipin is a type of fat or lipid in the body and an important
component of the inner mitochondrial membrane. Deficiency of
tafazzin activity affects remodelling with different types of
cardiolipin being produced. In Barth syndrome there are increased
levels of monolysocardiolipin (MLCL) and lower cardiolipin (L4-CL)
levels.
Urine organic acids: Testing for 3
-methylglutaconic acid (3-MGC) was used as the major biochemical
test for the disease until recent years. However, this test is now
considered unreliable, as it can sometimes be normal.
Cardiolipin analysis: Analysis of the
ratio of monolysocardiolipin (MLCL)/cardiolipin (CL) is the
diagnostic test of choice. Cardiolipin analysis on dried blood
spots is available in the UK at the Neurometabolic Unit, Institute
of Neurology, Queen Square. The test is free to UK NHS patients
suspected of having a diagnosis of Barth syndrome. Please see
details via the link below:
Bloodspot_cardiolipin_testing_information_September_2023.pdf
(uclh.nhs.uk)
Cardiolipin analysis on other tissues is possible but will incur
a charge. Please contact the Neurometabolic Unit to discuss.
Description of an intermediate form of Barth
syndrome: Cardiolipin testing discriminates
extremely well between normal boys and those with Barth
Syndrome. The Barth Syndrome Service have identified males from
three separate families who have higher cardiolipin levels than
most boys or men with the disease. In several cases this caused the
diagnosis to be missed on initial biochemical testing. Males with
this form of the disease on average appear to be more mildly
affected than the average person with Barth syndrome.
Post-mortem testing: If a patient is
suspected to have died as a result of Barth syndrome, cardiolipin
analysis can be performed in cultured fibroblasts (skin cells).
Please discuss with the Neurometabolic unit.
Genetic testing by TAZ Gene Sequencing: Further information on
genetic testing in Bristol and the proforma required is
given here.
Who to test
It has been estimated that between 3-5% of all young males
with dilated cardiomyopathy have Barth Syndrome as the cause of
their heart failure. This percentage may be even higher in
those who are in heart failure at birth or develop it within
the first year of life. We therefore recommend routine cardiolipin
testing in all young males with dilated cardiomyopathy. Cardiolipin
testing should also be considered in male babies/boys with
left ventricular noncompaction (LVNC), unexplained neutropenia
(especially with poor growth, developmental delay or weak muscles
and easy fatigability) and in families with a male pattern
of hypertrophic cardiomyopathy where no genetic cause can be
found and other features suggestive of Barth syndrome are
present.
