Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome.
Barth Syndrome (BTHS) is an X-linked recessive disorder that results in abnormal metabolism of the mitochondrial phospholipid cardiolipin (CL). CLs are decreased and monolysocardiolipins (MLCLs), intermediates in CL metabolism, are increased in a variety of tissues. Measurement of decreased CL levels in skin fibroblasts has previously been proposed as a diagnostic test for BTHS. We investigated whether elevated MLCL is specific for BTHS and whether the MLCL-to-CL ratio is a more sensitive and specific marker for BTHS. We measured CLs and MLCLs in skin fibroblasts from 5 BTHS patients, 8 controls, and 14 patients with biochemical and clinical findings similar to those in BTHS (group D), using high performance liquid chromatography-mass spectrometry. Our results showed a clear decrease of CL in combination with a marked increase of MLCL in fibroblasts from BTHS patients when compared with controls. MLCL/CL ratios ranged from 0.03-0.12 in control fibroblasts and from 5.41-13.83 in BTHS fibroblasts. In group D, the MLCL/CL ratio range was 0.02-0.06. We therefore conclude that elevations of MLCLs are specific for BTHS and that the MLCL/CL ratio in fibroblasts is a better diagnostic marker than CL alone. We also report the finding of two novel mutations in the TAZ gene that cause BTHS.
van Werkhoven
Michiel Adriaan
MA
Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, VIC 3052, Australia.
Thorburn
David Ross
DR
Gedeon
Agi Kyra
AK
Pitt
James Jonathon
JJ
D015415:Biomarkers / Q000032:analysis; D002308:Cardiolipins / Q000032:analysis*; D002460:Cell Line; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D005347:Fibroblasts / Q000737:chemistry* / Q000166:cytology; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000378:metabolism*; D006130:Growth Disorders / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008246:Lysophospholipids / Q000032:analysis*; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D013577:Syndrome
D015415:Biomarkers; D002308:Cardiolipins; D008246:Lysophospholipids; C067188:monolysocardiolipin