Human CoQ10 deficiencies
Human CoQ10 deficiencies
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DOI：
10.1002/biof.5520320113
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发表时间：
2008-01-01
期刊：
影响因子：
6
通讯作者：
Hirano, M.
中科院分区：
文献类型：
--
作者：
Quinzii, C. M.;Lopez, L. C.;Hirano, M.
辅酶Q（10）（CoQ（10）或泛醌）是几乎所有细胞膜的脂溶性组分，具有多种代谢功能。辅酶Q（10）的主要功能是在呼吸链中将电子从复合物I和H转运到复合物III，该呼吸链位于线粒体内膜中，（MIM 607426）与四种主要的临床表型相关：1）脑肌病，其特征在于复发性肌红蛋白尿、脑受累和破碎红纤维三联征; 2）婴儿多系统疾病，典型地具有显著的肾病和脑病; 3）小脑共济失调，具有显著的小脑萎缩;和4）单纯肌病。已在婴儿多系统性和小脑共济失调表型患者中发现了由于泛醌生物合成基因（COQ 2、PDSS 1、PDSS 2和ADCK 3 [CAB 1]）突变而导致的原发性CoQ（10）缺乏症。相反，继发性辅酶Q（10）缺乏，由于基因突变不直接相关的泛醌生物合成（APTX，ETFDH，BRAF），已确定在小脑共济失调，单纯性肌病，心面皮肤综合征的患者。在许多辅酶Q（10）缺乏症患者中，致病的分子遗传缺陷仍然未知;因此，其他基因的突变可能被确定为辅酶Q（10）缺乏症的原因。
Coenzyme Q(10) (CoQ(10) or ubiquinone) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. A major function of CoQ(10) is to transport electrons from complexes I and H to complex III in the respiratory chain which resides in the mitochondrial inner membrane, Deficiencies of CoQ(10) (MIM 607426) have been associated with four major clinical phenotypes: 1) encephalomyopathy characterized by a triad of recurrent myoglobinuria, brain involvement, and ragged-red fibers; 2) infantile multisystemic disease typically with prominent nephropathy and encephalopathy; 3) cerebellar ataxia with marked cerebellar atrophy; and 4) pure myopathy. Primary CoQ(10) deficiencies due to mutations in ubiquinone biosynthetic genes (COQ2, PDSS1, PDSS2, and ADCK3 [CABC1]) have been identified in patients with the infantile multisystemic and cerebellar ataxic phenotypes. In contrast, secondary CoQ(10) deficiencies, due to mutations in genes not directly related to ubiquinone biosynthesis (APTX, ETFDH, and BRAF), have been identified in patients with cerebellar ataxia, pure myopathy, and cardiofaciocutaneous syndrome. In many patients with CoQ(10) deficiencies, the causative molecular genetic defects remain unknown; therefore, it is likely that mutations in additional genes will be identified as causes of CoQ(10) deficiencies.