Barth syndrome without tetralinoleoyl cardiolipin deficiency: a possible ameliorated phenotype

Ann Bowron*, Julie Honeychurch, Maggie Williams, Beverley Tsai-Goodman, Nicol Clayton, Lucy Jones, Graham J. Shortland, Shakeel A. Qureshi, Simon J R Heales, Colin G. Steward

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)


Barth syndrome (BTHS) is an X-linked disorder characterised by cardiac and skeletal myopathy, growth delay, neutropenia and 3-methylglutaconic aciduria (3-MGCA). Patients have TAZ gene mutations which affect metabolism of cardiolipin, resulting in low tetralinoleoyl cardiolipin (CL4), an increase in its precursor, monolysocardiolipin (MLCL), and an increased MLCL/CL4 ratio. During development of a diagnostic service for BTHS, leukocyte CL4 was measured in 156 controls and 34 patients with genetically confirmed BTHS. A sub-group of seven subjects from three unrelated families was identified with leukocyte CL4 concentrations within the control range. This had led to initial false negative disease detection in two of these patients. MLCL/CL4 in this subgroup was lower than in other BTHS patients but higher than controls, with no overlap between the groups. TAZ gene mutations in these families are all predicted to be pathological. This report describes the clinical histories of these seven individuals with an atypical phenotype: some features were typical of BTHS (five have had cardiomyopathy, one family has a history of male infant deaths, three have growth delay and five have 3-MGCA) but none has persistent neutropenia, five have excellent exercise tolerance and two adults are asymptomatic. This report also emphasises the importance of measurement of MLCL/CL4 ratio rather than CL4 alone in the biochemical diagnosis of the BTHS.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalJournal of Inherited Metabolic Disease
Issue number2
Publication statusPublished - Mar 2015


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