Barth syndrome
Sarah Ln Clarke,Ann Bowron,Iris L. Gonzalez,Sarah J. Groves,Ruth Newbury-Ecob,Nicol Clayton,Robin P. Martin,Beverly Tsai-Goodman,Vanessa Garratt,Michael Ashworth,Valerie M. Bowen,Katherine R. McCurdy,Michaela K. Damin,Carolyn T. Spencer,Matthew J Toth,Richard I. Kelley,Colin G. Steward +16 more
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TLDR
The Barth syndrome (BTHS) is a rare X-linked genetic disease characterized by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA) as mentioned in this paper.Abstract:
First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.read more
Citations
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Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes
Špela Konjar,Špela Konjar,Ulrika C. Frising,Cristina Ferreira,Cristina Ferreira,Reinhard Hinterleitner,Toufic Mayassi,Qifeng Zhang,Birte Blankenhaus,Nejc Haberman,Yunhua Loo,Joana Guedes,Marta Baptista,Silvia Innocentin,Joerg Stange,Douglas Strathdee,Bana Jabri,Marc Veldhoen,Marc Veldhoen +18 more
TL;DR: It is shown that cardiolipin makeup can particularly restrict swift IEL proliferation and effector functions, reducing microbial containment capability, and a novel role for mitochondria is revealed, maintaining cells in a metabolically poised state while enabling rapid progression to full functionality.
Journal ArticleDOI
Molecular nature and physiological role of the mitochondrial calcium uniporter channel.
B. Rita Alevriadou,Akshar Patel,Megan Noble,Sagnika Ghosh,Vishal M. Gohil,Peter B. Stathopulos,Muniswamy Madesh +6 more
TL;DR: The structural details of the human MCU heteromeric assemblies and their known roles in regulating mitochondrial Ca2+ homeostasis and human disease pathogenesis are highlighted.
Journal ArticleDOI
Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.
Saskia B. Wortmann,Marc Espeel,Ligia Almeida,Annette G Reimer,Dennis Bosboom,Frank Roels,Arjan P.M. de Brouwer,Ron A. Wevers +7 more
TL;DR: An overview on both pathophysiology and the extremely heterogeneous clinical presentations of the disorders reported so far involved in the biosynthesis of phospholipids is provided.
Journal ArticleDOI
The functions of cardiolipin in cellular metabolism-potential modifiers of the Barth syndrome phenotype.
TL;DR: Understanding the role of CL in energy metabolism may identify physiological modifiers that exacerbate the loss of CL and underlie the variation in symptoms observed in Barth syndrome, a genetic disorder of CL metabolism.
Journal ArticleDOI
The Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes.
TL;DR: This review aims to provide an understanding of the biological mechanisms that link mitochondria dynamics and mtDNA integrity, as well as examine the interplay that occurs between mtDNA, mitochondrial dynamics and cristae structure.
References
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Journal ArticleDOI
The biosynthesis and functional role of cardiolipin.
Journal ArticleDOI
A novel X-linked gene, G4.5. is responsible for Barth syndrome
Silvia Bione,Patrizia D'Adamo,Elena Maestrini,Agi K. Gedeon,Pieter A. Bolhuis,Daniela Toniolo +5 more
TL;DR: The results suggest that G4.5 is the genetic locus responsible for the Barth syndrome, and introduces stop codons in the open reading frame interrupting translation of most of the putative proteins.
Journal ArticleDOI
An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes
Peter G. Barth,Hans R. Scholte,J.A. Berden,J.M. Van Der Klei-Van Moorsel,I.E.M. Luyt-Houwen,E.Th. Van'T Veer-Korthof,J.J. Van Der Harten,M.A. Sobotka-plojhar +7 more
TL;DR: Biochemical studies and haematological abnormalities (neutropenia) are reported for the first time in an X-linked recessive disease reported in a large pedigree of boys.
Journal ArticleDOI
The epidemiology of childhood cardiomyopathy in Australia.
Alan Nugent,Piers E.F. Daubeney,Patty Chondros,John B. Carlin,Michael Cheung,Lynette C. Wilkinson,Andrew M. Davis,Stephen G. Kahler,Chung Wo Chow,James L. Wilkinson,Robert G. Weintraub +10 more
TL;DR: The timing and severity of presentation in children with cardiomyopathy are related to the type of cardiomeopathy, as well as to genetic and ethnic factors.
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Clinical Characterization of Left Ventricular Noncompaction in Children A Relatively Common Form of Cardiomyopathy
Ricardo H. Pignatelli,Colin J. McMahon,William J. Dreyer,Susan W. Denfield,Jack F. Price,John W. Belmont,William J. Craigen,Jen Wu,Howaida G. El Said,Louis I. Bezold,Sarah K. Clunie,Susan D. Fernbach,Neil E. Bowles,Jeffrey A. Towbin +13 more
TL;DR: A significant number of patients with LVNC have transient recovery of function followed by later deterioration, which may account for many patients presenting as adults, some manifesting an “undulating” phenotype.