Barth syndrome.
Barth syndrome.
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DOI：
10.1186/1750-1172-8-23
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发表时间：
2013-02-12
影响因子：
3.7
通讯作者：
Steward CG
中科院分区：
文献类型：
--
作者：
Clarke SL;Bowron A;Gonzalez IL;Groves SJ;Newbury-Ecob R;Clayton N;Martin RP;Tsai-Goodman B;Garratt V;Ashworth M;Bowen VM;McCurdy KR;Damin MK;Spencer CT;Toth MJ;Kelley RI;Steward CG
Barth综合征（BTHS）于1983年首次被描述，被广泛认为是一种罕见的X连锁遗传疾病，其特征为心肌病（CM）、骨骼肌病、生长迟缓、中性粒细胞减少和3-甲基戊烯二酸（3-MGCA）的尿排泄增加。全世界已知的在世男性不到200例，但越来越多的证据表明，这种疾病的诊断严重不足。临床特征包括以下广谱疾病的可变组合：扩张型心肌病（DCM）、肥厚型心肌病（HCM）、内皮型弹力纤维增生症（EFE）、左心室致密化不全（LVNC）、室性心律失常、心源性猝死、QTc间期延长、运动里程碑延迟、近端肌病、嗜睡和疲乏、中性粒细胞减少症（不存在至严重;持续性、间歇性或完全周期性）、代偿性单核细胞增多症、复发性细菌感染、低血糖、乳酸性酸中毒、生长和青春期延迟、喂养问题、发育不良、间歇性腹泻、特征性面容，和X连锁家族史BTHS在历史上被认为是一种心脏病，现在被认为是一种多系统疾病，可能首先被许多不同的专家或通才发现。表型宽度和变异性对诊断医生提出了一个主要挑战：一些BTHS儿童从未出现过血小板减少，而另一些儿童缺乏增加的3-MGCA，少数儿童有隐匿性或不存在CM。此外，BTHS在2010年首次被描述为胎儿死亡的未识别原因。位于Xq 28的tafazzin（TAZ）基因的失能突变或缺失通过减少心磷脂（线粒体内膜的主要磷脂）的重塑而引起疾病。2008年首次描述了一种基于检测不同心磷脂种类的异常比率的确定性生化测试。鉴别诊断的关键领域包括代谢性和病毒性心肌病、线粒体疾病以及中性粒细胞减少症和复发性男性流产和死产的许多原因。心磷脂测试和TAZ测序现在提供相对快速的诊断测试，前瞻性和回顾性，从一系列新鲜或储存的组织，血液或新生儿血斑。TAZ测序还允许女性携带者检测和产前筛查。BTHS的管理包括CM的药物治疗，心脏移植（14%的患者），抗生素预防和粒细胞集落刺激因子（G-CSF）治疗。多学科团队/诊所对于最大限度地减少医院就诊率和让更多的BTHS患者活到成年至关重要。
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.
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影响因子：
4.8
作者：
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通讯作者：
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30.8
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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