Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome

Michiel Adriaan Van Werkhoven, David Ross Thorburn, Agi Kyra Gedeon, James Jonathon Pitt

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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.

Original languageEnglish
Pages (from-to)2346-2351
Number of pages6
JournalJournal of Lipid Research
Volume47
Issue number10
DOIs
Publication statusPublished - 1 Oct 2006

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Barth Syndrome
Cardiolipins
Fibroblasts
Metabolism
Skin
monolysocardiolipin
High performance liquid chromatography
Mass spectrometry
Routine Diagnostic Tests
Phospholipids

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Van Werkhoven, Michiel Adriaan ; Thorburn, David Ross ; Gedeon, Agi Kyra ; Pitt, James Jonathon. / Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome. In: Journal of Lipid Research. 2006 ; Vol. 47, No. 10. pp. 2346-2351.
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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.",
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Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome. / Van Werkhoven, Michiel Adriaan; Thorburn, David Ross; Gedeon, Agi Kyra; Pitt, James Jonathon.

In: Journal of Lipid Research, Vol. 47, No. 10, 01.10.2006, p. 2346-2351.

Research output: Contribution to journalArticle

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T1 - Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome

AU - Van Werkhoven, Michiel Adriaan

AU - Thorburn, David Ross

AU - Gedeon, Agi Kyra

AU - Pitt, James Jonathon

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AB - 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.

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