Table 3 Diagnostic tests for BTHS

Urinary 3-MGCA Testing

Most cases of BTHS will be suggested by the finding of a 5-20 fold elevation of 3-MGC excretion on quantitative urinary organic acid analysis. As this test is non-specific, confirmation of the diagnosis is required by TAZ mutation/cardiolipin ratio testing.

N.B. Multiple reports suggest that urinary 3-MGCA levels may be normal on single specimen testing in patients later shown to have BTHS[45, 50, 61, 65–67]. A negative 3-MGCA test in a candidate patient must therefore be confirmed by cardiolipin ratio testing or TAZ sequencing in order to reliably exclude BTHS.

Monolysocardiolipin/Cardiolipin (MLCL:L4-CL) Ratio Testing (where available)

This test offers the best combination of speed, cost and diagnostic accuracy, with 100% diagnostic sensitivity and specificity reported in several series, but is currently only available in a few laboratories[7, 28, 78].

Testing can be performed on blood specimens (sent by routine postal services), stored tissue or dried blood spots.

TAZ Gene Sequencing:

TAZ gene sequencing can be targeted selectively to those with an abnormal cardiolipin ratio test or performed in all candidate patients where cardiolipin testing is not available. It is increasingly being offered as one of the genes sequenced simultaneously in sequencing panels for investigation of cardiomyopathy. It also has an important place in the investigation of patients/families where appropriate samples for biochemical testing are not available from suspected index patients.