title: Barth syndrome without tetralinoleoyl cardiolipin deficiency: a possible ameliorated phenotype.
abstract: 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 (CL(4)), an increase in its precursor, monolysocardiolipin (MLCL), and an increased MLCL/CL(4) ratio. During development of a diagnostic service for BTHS, leukocyte CL(4) 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 CL(4) concentrations within the control range. This had led to initial false negative disease detection in two of these patients. MLCL/CL(4) 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/CL(4) ratio rather than CL(4) alone in the biochemical diagnosis of the BTHS.
authors.affiliation: Department of Clinical Biochemistry, University Hospitals Bristol NHS Trust, Bristol, BS2 8HW, UK, ann.bowron@bristol.ac.uk.
authors.forename: Ann
authors.initials: A
authors.lastname: Bowron
authors.forename: Julie
authors.initials: J
authors.lastname: Honeychurch
authors.forename: Maggie
authors.initials: M
authors.lastname: Williams
authors.forename: Beverley
authors.initials: B
authors.lastname: Tsai-Goodman
authors.forename: Nicol
authors.initials: N
authors.lastname: Clayton
authors.forename: Lucy
authors.initials: L
authors.lastname: Jones
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Shortland
authors.forename: Shakeel A
authors.initials: SA
authors.lastname: Qureshi
authors.forename: Simon J R
authors.initials: SJ
authors.lastname: Heales
authors.forename: Colin G
authors.initials: CG
authors.lastname: Steward
mesh_terms: D000217:Acyltransferases; D000293:Adolescent; D000328:Adult; D056889:Barth Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D002308:Cardiolipins / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005188:False Negative Reactions; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D014157:Transcription Factors / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D002308:Cardiolipins; D014157:Transcription Factors; C523441:tetralinoleoylcardiolipin; D000217:Acyltransferases; C108675:TAFAZZIN protein, human
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