Barth Syndrome with Late-Onset Cardiomyopathy: A Missed Opportunity for Diagnosis

Woiewodski, Leanne; Ezon, David; Cooper, James; Feingold, Brian

doi:10.1016/j.jpeds.2016.12.070

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…Barth syndrome (BTHS) is an X-linked recessive multisystem disorder associated with cardiomyopathy, neutropenia, exercise intolerance, sudden cardiac death, skeletal muscle weakness, recurrent bacterial infections and growth delay [1,2]. The approximated BTHS prevalence of 1/300,000-400,000 live births [1,3] is likely underestimated since the disorder is substantially under-diagnosed [1,4]. BTHS is caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) [5], which encodes for the acyltransferase tafazzin.…”

Section: Introductionmentioning

confidence: 99%

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

et al. 2019

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Barth syndrome (BTHS) is an X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. This protein is highly expressed in the heart and plays a significant role in cardiolipin biosynthesis. Heart disease is the major clinical manifestation of BTHS with a high incidence in early life. Although the genetic basis of BTHS and tetralinoleoyl cardiolipin deficiency in BTHS-affected individuals are well-established, downstream metabolic changes in cardiac metabolism are still uncovered. Our study aimed to characterize TAZ-induced metabolic perturbations in the heart. Control (PGP1-TAZWT) and TAZ mutant (PGP1-TAZ517delG) iPS-CM were incubated with 13C6-glucose and 13C5-glutamine and incorporation of 13C into downstream Krebs cycle intermediates was traced. Our data reveal that TAZ517delG induces accumulation of cellular long chain acylcarnitines and overexpression of fatty acid binding protein (FABP4). We also demonstrate that TAZ517delG induces metabolic alterations in pathways related to energy production as reflected by high glucose uptake, an increase in glycolytic lactate production and a decrease in palmitate uptake. Moreover, despite mitochondrial dysfunction, in the absence of glucose and fatty acids, TAZ517delG-iPS-CM can use glutamine as a carbon source to replenish the Krebs cycle.

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Section: Introductionmentioning

confidence: 99%

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

et al. 2019

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“…Cardiac abnormalities may be more prevalent if LVHT is present. Only rarely, cardiomyopathy may develop late in the disease course40 or patients may not develop cardiomyopathy at all 25. Cardioembolism may be complicated by embolic stroke or occlusion of peripheral arteries.…”

Section: Resultsmentioning

confidence: 99%

<p>Barth syndrome: mechanisms and management</p>

Finsterer¹

2019

TACG

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Objectives: Barth syndrome is an ultra-rare, infantile-onset, X-linked recessive mitochondrial disorder, primarily affecting males, due to variants in TAZ encoding for the cardiolipin transacylase tafazzin. This review aimed to summarize and discuss recent and earlier findings concerning the etiology, pathogenesis, clinical presentation, diagnosis, treatment, and outcome of Barth syndrome. Method: A literature review was undertaken through a MEDLINE search. Results: The phenotype of Barth syndrome is highly variable but most frequently patients present with hypertrophic/dilated/non-compaction cardiomyopathy, fibroelastosis, arrhythmias, neutropenia, mitochondrial myopathy, growth retardation, dysmorphism, cognitive impairment, and other, rarer features. Lactic acid and creatine kinase, and blood and urine organic acids, particularly 3-methylglutaconic acid and monolysocardiolipin, are often elevated. Cardiolipin is decreased. Biochemical investigations may show decreased activity of various respiratory chain complexes. The diagnosis is confirmed by documentation of a causative TAZ variant. Treatment is symptomatic and directed toward treating heart failure, arrhythmias, neutropenia, and mitochondrial myopathy. Conclusions: Although Barth syndrome is still an orphan disease, with fewer than 200 cases described so far, there is extensive ongoing research with regard to its pathomechanism and new therapeutic approaches. Although most of these approaches are still experimental, it can be expected that causative strategies will be developed in the near future.

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“…33 Furthermore, we strongly advocate for lifelong cardiac monitoring of all individuals with Barth syndrome, including those who demonstrate extended recovery. We make this recommendation given that: 1) relatively little is known about specific triggers for cardiac dysfunction in Barth syndrome, 2) late childhood onset cardiac dysfunction with severe heart failure with evidence of prior normal echocardiography has been reported in Barth syndrome, 6 and 3) the relationship of arrhythmic sudden death with ventricular function/heart failure in Barth syndrome is not currently understood but potentially widely impactful for individuals with Barth syndrome.…”

Section: Discussionmentioning

confidence: 99%

Extended recovery of cardiac function after severe infantile cardiomyopathy presentation of Barth syndrome

Yester

Feingold

2021

JIMD Reports

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Cardiomyopathy is the most common presenting feature of Barth syndrome, often presenting in infancy with severe heart failure and cardiac dysfunction.Historically, affected infants commonly died early after presentation, sometimes before a diagnosis of Barth syndrome was made. With increases in awareness of Barth syndrome and in the care of infants with severe heart failure, survival of children with Barth syndrome and severe heart failure has improved. We describe our experience caring for five unrelated boys with Barth syndrome who presented with severe cardiomyopathy and heart failure prior to age 2 who have had marked improvement with long-term response to medical heart failure therapy.

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Barth Syndrome with Late-Onset Cardiomyopathy: A Missed Opportunity for Diagnosis

Cited by 11 publications

References 19 publications

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

<p>Barth syndrome: mechanisms and management</p>

Extended recovery of cardiac function after severe infantile cardiomyopathy presentation of Barth syndrome

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