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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Journal ArticleDOI
Barth Syndrome: From Mitochondrial Dysfunctions Associated with Aberrant Production of Reactive Oxygen Species to Pluripotent Stem Cell Studies.
TL;DR: Recent results of studies on various animal or cell models of Barth syndrome, which have characterized biochemically the strong cellular defects associated with TAZ mutations, are summarized to evaluate potential therapies with the use of mitochondrially targeted antioxidants.
Journal ArticleDOI
The ionization properties of cardiolipin and its variants in model bilayers.
TL;DR: The ionization properties of cardiolipin within biologically relevant lipid bilayer model systems are analyzed and it is indicated that within the physiological pH range, the cardiolIPin headgroup is fully ionized as a dianion.
Journal ArticleDOI
Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients
Alireza Haghighi,Alireza Haghighi,Tobias B. Haack,Mehnaz Atiq,Hassan Mottaghi,Hamidreza Haghighi-Kakhki,Rani A Bashir,Uwe Ahting,René G. Feichtinger,Johannes A. Mayr,Agnès Rötig,Anne-Sophie Lebre,Thomas Klopstock,Andrea Dworschak,Nathan Pulido,Mahmood A Saeed,Nasrollah Saleh-Gohari,Eliška Holzerová,Patrick F. Chinnery,Robert W. Taylor,Holger Prokisch +20 more
TL;DR: It is confirmed that Sengers syndrome is a clinically recognisable disorder of mitochondrial energy metabolism and mitochondrial DNA content was normal in both tissues.
Journal ArticleDOI
Development of pharmacological strategies for mitochondrial disorders
TL;DR: Improved understanding of mitochondrial pathways and the development of many animal models are facilitating the discovery and evaluation of novel prospective treatments, and increasing mitochondrial biogenesis, whether by pharmacological approaches, dietary manipulation or exercise therapy, is also currently an active area of research.
Journal ArticleDOI
Barth Syndrome: Connecting Cardiolipin to Cardiomyopathy
Nikita Ikon,Robert O. Ryan +1 more
TL;DR: Prolonged deficiency in ATP production capacity underlies cell and tissue pathology that ultimately is manifest as dilated cardiomyopathy.
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.
Journal ArticleDOI
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.