A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder
A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder
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DOI：
10.1177/0883073816666221
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发表时间：
2017-02-01
影响因子：
1.9
通讯作者：
Hirano, Michio
中科院分区：
文献类型：
--
作者：
Garone, Caterina;Gurgel-Giannetti, Juliana;Hirano, Michio
SUCLA2 缺陷与线粒体 DNA (mtDNA) 耗竭以及肌张力减退、肌张力障碍/Leighlike 综合征和耳聋三联征有关。一名近亲父母的 9 岁巴西男孩出现精神运动迟缓、耳聋、肌病、共济失调和舞蹈症。尽管存在明显的运动障碍，但脑磁共振成像（MRI）正常，而 1 H 磁共振波谱（MRS）显示大脑皮层和侧脑室出现乳酸峰值。在肌肉和成纤维细胞中观察到含有 mtDNA 编码亚基的线粒体呼吸链酶的生化活性降低和 mtDNA 耗竭。鉴定出 SUCLA2 中的一个新的纯合突变，该突变是该蛋白的连接酶辅酶 A (CoA) 结构域中的第一个突变。将 CoQ10 剂量逐渐增加至每天 2000 毫克与肌无力的改善和病程的稳定相关。研究结果表明，在没有脑 MRI 病变的复杂运动障碍患者中筛查线粒体功能障碍，并进一步研究 SUCLA2 突变患者中潜在的继发性辅酶 Q10 缺乏症具有重要意义。
SUCLA2 defects have been associated with mitochondrial DNA (mtDNA) depletion and the triad of hypotonia, dystonia/ Leighlike syndrome, and deafness. A 9-year-old Brazilian boy of consanguineous parents presented with psychomotor delay, deafness, myopathy, ataxia, and chorea. Despite the prominent movement disorder, brain magnetic resonance imaging (MRI) was normal while 1 H-magnetic resonance spectroscopy (MRS) showed lactate peaks in the cerebral cortex and lateral ventricles. Decreased biochemical activities of mitochondrial respiratory chain enzymes containing mtDNA-encoded subunits and mtDNA depletion were observed in muscle and fibroblasts. A novel homozygous mutation in SUCLA2, the first one in the ligase coenzyme A (CoA) domain of the protein, was identified. Escalating doses of CoQ10 up to 2000 mg daily were associated with improvement of muscle weakness and stabilization of the disease course. The findings indicate the importance of screening for mitochondrial dysfunction in patients with complex movement disorders without brain MRI lesions and further investigation for potential secondary CoQ10 deficiency in patients with SUCLA2 mutations.