X-linked cardioskeletal myopathy and neutropenia (Barth syndrome)—MIM 302060

Barth, P. G.; Wanders, Ronald J. A.; Vreken, P.

doi:10.1016/s0022-3476(99)70118-6

Cited by 100 publications

(88 citation statements)

References 33 publications

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“…Thus, definite conclusions about the mitochondrial pathology could not be drawn, although it appeared that the mitochondrial dysfunction was not caused by a defect in any specific respiratory enzyme. 3 This concept was consistent with the lipid etiology of BTHS. 6,7,9 Since phospholipids form the general environment of membrane proteins, they may influence the performance of multiple respiratory enzymes.…”

Section: Discussionsupporting

confidence: 70%

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Characterization of lymphoblast mitochondria from patients with Barth syndrome

Sutachán

Plesken

et al. 2005

Laboratory Investigation

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Barth syndrome (BTHS) is a multisystem disorder of individuals who carry mutations in tafazzin, a putative phospholipid acyltransferase. We investigated the hypothesis that BTHS is caused by specific impairment of the mitochondrial lipid metabolism. The fatty acid composition of all major mitochondrial phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), changed in lymphoblasts from BTHS patients. These changes were most extensive in CL and least extensive in PE. The complementary nature of the fatty acid alterations in CL and PC suggested that fatty acid transfer between these two lipids was inhibited in BTHS. Fluorescence staining and electron microscopy showed abnormal proliferation of mitochondria in BTHS lymphoblasts. The mitochondrial membrane potential, monitored with the fluorescence probe JC-1, was reduced in BTHS lymphoblasts. However, mitochondrial ATP formation of permeabilized lymphoblasts remained unaffected in BTHS. The data suggest that phospholipid abnormalities of BTHS mitochondria led to partial uncoupling of oxidative phosphorylation and that lymphoblasts compensated for this deficiency by expanding the mitochondrial compartment.

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Section: Discussionsupporting

confidence: 70%

“…[1][2][3][4] Mutations that cause BTHS are located in the tafazzin gene, 5 which belongs to a large superfamily of phospholipid acyltransferases. 6 The lipid etiology of BTHS was confirmed when Vreken et al 7 found aberrant cardiolipin (CL) metabolism in BTHS fibroblasts.…”

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confidence: 99%

Characterization of lymphoblast mitochondria from patients with Barth syndrome

Sutachán

Plesken

et al. 2005

Laboratory Investigation

132

128

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“…It is characterized by cardiomyopathy, neutropenia, skeletal myopathy, and growth retardation (plus frequent striking catch-up growth during adolescence) (1)(2)(3)(4)(5)(6)(7). Other biochemical characteristics include 3-methylglutaconic, 3-methylglutaric, and 2-ethylhydracrylic aciduria (1,2,6,8 ), low cholesterol (6,7 ), and abnormal mitochondria (7,9,10 ).…”

Section: Barth Syndrome (Bths)mentioning

confidence: 99%

“…We established instrument variation by analyzing 10 consecutive injections of the same sample. As a measure of the overall variation in absolute response of the LC-MS/MS, we monitored the peak area of the CL internal standard CL(14:0) 4 . Intraassay CV was determined by multiple analyses of bloodspots of each of 3 different BTHS patients and 3 controls within the same series.…”

Section: Validationmentioning

confidence: 99%

“…The gradient separated CL and MLCL from other phospholipids, thus minimizing interference and suppression of signal of the analytes while maximizing signal-to-noise ratio (S/N) for both MLCL and CL, under similar conditions in a reduced runtime. LC-MS analysis of dried bloodspots showed tetralinoleonylcardiolipin [CL (18:2) 4 had the best S/N in dried bloodspot extracts for the transition m/z 619.9 3 m/z 227.2 (C14:0). Reported data are based on the measurement of peak area of the chromatographic peaks of the optimized MRM transitions.…”

Section: Hplc-ms/msmentioning

confidence: 99%

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Bloodspot Assay Using HPLC–Tandem Mass Spectrometry for Detection of Barth Syndrome

et al. 2008

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Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)

et al. 2001

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An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.

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X-linked cardioskeletal myopathy and neutropenia (Barth syndrome)—MIM 302060

Cited by 100 publications

References 33 publications

Characterization of lymphoblast mitochondria from patients with Barth syndrome

Characterization of lymphoblast mitochondria from patients with Barth syndrome

Bloodspot Assay Using HPLC–Tandem Mass Spectrometry for Detection of Barth Syndrome

Barth's syndrome-like disorder: A new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation)

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