Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II) with a novel mutation of electron transfer flavoprotein-dehydrogenase in a cat.
Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II) with a novel mutation of electron transfer flavoprotein-dehydrogenase in a cat.
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猫体内多种酰基辅酶A脱氢缺陷（II型戊二酸尿症），伴有电子转移黄素蛋白脱氢酶的新突变。
DOI：
10.1007/8904_2013_268
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Nishino K.
中科院分区：
文献类型：
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作者：
Wakitani S;Torisu S;Yoshino T;Hattanda K;Yamato O;Tasaki R;Fujita H;Nishino K.
多发性酰基辅酶a脱氢缺乏症（MADD，又称戊二酸尿症II型）是一种人类常染色体隐性遗传病，属于线粒体脂肪酸氧化障碍之一。MADD是由电子转移黄蛋白（ETF）或ETF脱氢酶（ETFDH）分子缺陷引起的，但到目前为止，在动物中尚未见遗传性MADD的报道。在此，我们首次报道了猫的MADD。患病动物表现为低血糖、高氨血症、呕吐、诊断性有机酸尿、血浆中长链脂肪酸积累等MADD的典型症状。核黄素和左旋肉碱治疗可改善症状。为了检测该病例中导致MADD的基因突变，我们测定了猫ETFα、ETFβ和ETFDH的完整cDNA序列。最后，我们在ETFDH中发现了猫患者特异性突变c.692T>G （p.F231C）。患病动物仅携带ETFDH突变等位基因。猫ETFDH中的p.F231在真核生物中完全保守，位于ETFDH的顶表面，接受来自ETF的电子。因此，这项研究确定了强烈怀疑是这只猫的MADD病因的突变。
Multiple acyl-CoA dehydrogenation deficiency (MADD; also known as glutaric aciduria type II) is a human autosomal recessive disease classified as one of the mitochondrial fatty-acid oxidation disorders. MADD is caused by a defect in the electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH) molecule, but as yet, inherited MADD has not been reported in animals. Here we present the first report of MADD in a cat. The affected animal presented with symptoms characteristic of MADD including hypoglycemia, hyperammonemia, vomiting, diagnostic organic aciduria, and accumulation of medium- and long-chain fatty acids in plasma. Treatment with riboflavin andl-carnitine ameliorated the symptoms. To detect the gene mutation responsible for MADD in this case, we determined the complete cDNA sequences of feline ETFα, ETFβ, and ETFDH. Finally, we identified the feline patient-specific mutation, c.692T>G (p.F231C) in ETFDH. The affected animal only carries mutant alleles of ETFDH. p.F231 in feline ETFDH is completely conserved in eukaryotes, and is located on the apical surface of ETFDH, receiving electrons from ETF. This study thus identified the mutation strongly suspected to have been the cause of MADD in this cat.