Cavitating leukoencephalopathy with multiple mitochondrial dysfunction syndrome and NFU1 mutations
Cavitating leukoencephalopathy with multiple mitochondrial dysfunction syndrome and NFU1 mutations
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DOI：
10.3389/fgene.2014.00412
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发表时间：
2014-11-20
影响因子：
3.7
通讯作者：
Moroni, Isabella
中科院分区：
文献类型：
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作者：
Invernizzi, Federica;Ardissone, Anna;Moroni, Isabella
多发性线粒体功能障碍综合征（Multiple Mitochondrial Dysfunction Syndrome，MMDS）是一组严重的常染色体隐性遗传疾病，发病于婴儿早期，以全身性能量代谢紊乱为特征，导致虚弱、呼吸衰竭、神经系统发育障碍、乳酸酸中毒和早死。生化检查结果包括线粒体呼吸链复合物I、II和III的缺陷和丙酮酸脱氢酶复合物（PDHc）的严重缺乏。迄今为止，已有三个基因与MMDS相关：NFU 1、BOLA 3和IBA 57。我们描述了一个意大利男性患者出现严重的精神退行性疾病后，感染发作，乳酸酸中毒，高甘氨酸血症，减少呼吸链复合物II与PDHc活性的显着不足。他在NFU1中携带两个杂合突变，一个是新的（p.Cys210Phe），一个是先前报道的（p.Gly189Arg）错义变化，影响高度保守的残基。脑MRI显示一个严重的白质脑病伴深部白色物质空洞，提示一种与该基因缺陷相关的特殊神经放射学表型。
Multiple Mitochondrial Dysfunction Syndrome (MMDS) comprises a group of severe autosomal recessive diseases with onset in early infancy and characterized by a systemic disorder of energy metabolism, resulting in weakness, respiratory failure, lack of neurological development, lactic acidosis, and early death. Biochemical findings include defects of complexes I, II, and III of the mitochondrial respiratory chain and severe deficiency of Pyruvate dehydrogenase complex (PDHc). Three genes have been associated with MMDS since now: NFU1, BOLA3, and IBA57. We describe an Italian male patient presenting with severe psychomotor regression after an infectious episode, lactic acidosis, hyperglycinemia, reduction of respiratory chain complex II associated with a marked deficiency of PDHc activity. He carried two heterozygous mutations in NFUl, one novel (p.Cys210Phe) and one previously reported (p.Gly189Arg) missense change affecting highly conserved residues. A severe leukoencephalopathy with cavitations in deep white matter was disclosed at brain MRI, suggesting a peculiar neuroradiological phenotype associated with defect in this gene.