出版社：American Society for Biochemistry and Molecular Biology
摘要：Barth Syndrome (BTHS) is an X-linked recessive disorder thatresults in abnormal metabolism of the mitochondrial phospholipidcardiolipin (CL). CLs are decreased and monolysocardiolipins(MLCLs), intermediates in CL metabolism, are increased in avariety of tissues. Measurement of decreased CL levels in skinfibroblasts has previously been proposed as a diagnostic testfor BTHS. We investigated whether elevated MLCL is specificfor BTHS and whether the MLCL-to-CL ratio is a more sensitiveand specific marker for BTHS. We measured CLs and MLCLs in skinfibroblasts from 5 BTHS patients, 8 controls, and 14 patientswith biochemical and clinical findings similar to those in BTHS(group D), using high performance liquid chromatography-massspectrometry. Our results showed a clear decrease of CL in combinationwith a marked increase of MLCL in fibroblasts from BTHS patientswhen compared with controls. MLCL/CL ratios ranged from 0.03–0.12in control fibroblasts and from 5.41–13.83 in BTHS fibroblasts.In group D, the MLCL/CL ratio range was 0.02–0.06. Wetherefore conclude that elevations of MLCLs are specific forBTHS and that the MLCL/CL ratio in fibroblasts is a better diagnosticmarker than CL alone. We also report the finding of two novelmutations in the TAZ gene that cause BTHS.Supplementary key words tandem-mass spectrometry • cardiomyopathy • tafazzin
Abbreviations: BTHS, Barth Syndrome; CL, cardiolipin; MLCL, monolysocardiolipin; m/z–, mass-to-charge ratio, negative ion mode; TAZ, tafazzin
