title: Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome.
abstract: 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.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, VIC 3052, Australia.
authors.forename: Michiel Adriaan
authors.initials: MA
authors.lastname: van Werkhoven
authors.forename: David Ross
authors.initials: DR
authors.lastname: Thorburn
authors.forename: Agi Kyra
authors.initials: AK
authors.lastname: Gedeon
authors.forename: James Jonathon
authors.initials: JJ
authors.lastname: Pitt
mesh_terms: 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
chemical_list: D015415:Biomarkers; D002308:Cardiolipins; D008246:Lysophospholipids; C067188:monolysocardiolipin