X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060)
X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060)
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DOI：
10.1023/a:1005568609936
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发表时间：
1999-06-01
影响因子：
4.2
通讯作者：
Baas, F
中科院分区：
文献类型：
--
作者：
Barth, PG;Wanders, RJA;Baas, F
在欧洲、北美和澳大利亚的患者和家族中报告了X连锁心脏骨骼肌病、中性粒细胞减少症和异常线粒体（MIM 302060）（同义词：Barth综合征、3-甲基戊烯二酸尿症II型、内皮细胞弹性纤维增生症2型）。以前的研究特征的疾病的主要组成部分：扩张型心肌病，骨骼肌病，中性粒细胞减少症，3-甲基戊烯二酸尿症和减少身高增长。在几项研究中发现了呼吸链损伤，但没有确定单一的酶复合物。3-甲基戊烯二酸尿症与其他几种影响呼吸链的疾病相同。先前的研究排除了亮氨酸催化剂的主要途径中的阻断。我们对患者进行了亮氨酸负荷，并伴有禁食，观察到3-甲基戊烯二酸和3-甲基戊二酸的显著升高。结合主要亮氨酸分解代谢途径中酶促阻断的缺失，3-甲基戊烯二酸和支链氨基酸的其他产物的基础排泄增加可能是该途径过载的结果，或者更可能是线粒体渗漏。连锁研究已将该基因定位于Xq 28区域。相关的tafazzin基因（TAZ），最近已被充分表征，并已报道位于保守区域的突变。现在，通过突变分析，携带者检测和产前诊断已成为可能。TAZ基因与高度保守的酰基转移酶超类的序列同源性（Neuwald假说）预测甘油磷脂是缺失的终产物。这表明线粒体内膜的（脂质）结构是一个有前途的新研究领域。
X-linked cardioskeletal myopathy, neutropenia and abnormal mitochondria (MIM 302060) (synonyms: Barth syndrome, 3-methylglutaconic aciduria type II, endocardial fibroelastosis type 2) has been reported in patients and families from Europe, North America and Australia. Previous studies characterized the main components of the disease: dilated cardiomyopathy, skeletal myopathy, neutropenia, 3-methylglutaconic aciduria and diminished statural growth. Respiratory chain impairments have been found in several studies, without pinpointing a single enzyme complex. 3-Methylglutaconic aciduria is shared with several other disorders that affect the respiratory chain. Previous studies excluded a block in the major pathway of leucine catabolism. We performed leucine loading, accompanied by fasting, in patients and observed a significant rise of 3-methylglutaconic acid and 3-methylglutaric acid. Taken together with the absence of an enzymatic block in the major leucine catabolic route, the possibility remains that the increased basal excretion of 3-methylglutaconic acid and other products of branched-chain amino acids is the result of overload of this pathway or-more likely-mitochondrial leakage. Linkage studies have localized the gene to the Xq28 region. The associated tafazzin gene (TAZ), has been fully characterized recently, and mutations located in conserved regions have been reported. Carrier detection and prenatal diagnosis have now become possible through mutation analysis. Sequence homology of the TAZ gene to a highly conserved superclass of acyltransferases (Neuwald's hypothesis) predicts a glycerophospholipid as the missing end product. This points to the (lipid) structure of the inner mitochondrial membrane as a promising new area of research.