Prospective diagnosis of MT-ATP6-related mitochondrial disease by newborn screening.
Prospective diagnosis of MT-ATP6-related mitochondrial disease by newborn screening.
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新生儿筛查对MT-ATP6相关线粒体疾病的前瞻性诊断
DOI：
10.1016/j.ymgme.2021.06.007
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发表时间：
2021-09
影响因子：
3.8
通讯作者：
Ganetzky RD
中科院分区：
文献类型：
--
作者：
Peretz RH;Ah Mew N;Vernon HJ;Ganetzky RD
在推荐的统一筛查小组(RUSP)上，瓜氨酸和C5-OH水平升高被报告为新生儿核心和继发性疾病筛查的一部分。此外，一些州立实验室新生儿筛查项目报告了低瓜氨酸水平，这可能在近端尿素循环障碍中观察到。我们报告了在新生儿筛查中发现的6名患者，他们有低瓜氨酸和/或高C5-OH水平，在这些患者中，确证测试显示这两种异常分析的组合。线粒体测序显示MT-ATP6的已知致病变异在所有病例中都处于高异质性水平。这些异质性水平的MT-ATP6与Leigh综合征有关，Leigh综合征是一种进行性神经退行性疾病。患者接受补充瓜氨酸的治疗，在某些情况下，还接受线粒体辅因子治疗。这6名患者没有经历过代谢危机或发育退化，早期诊断和处理可能有助于预防Leigh综合征的神经后遗症。受影响的母亲和兄弟姐妹没有症状或缺乏症状(例如智力残疾、抑郁症、偏头痛、强迫症和平衡不良)，尽管家族性变异具有高度的异质性或明显的同质性，因此扩大了MT-ATP6致病变异的临床谱系。对于低瓜氨酸和/或C5-OH升高的患者，应进行验证性血浆氨基酸分析和酰肉碱分析，因为这种组合似乎对MT-ATP6的致病变异具有特异性。
Elevated citrulline and C5-OH levels are reported as part of the newborn screening of core and secondary disorders on the Recommended Uniform Screening Panel (RUSP). Additionally, some state laboratory newborn screening programs report low citrulline levels, which may be observed in proximal urea cycle disorders. We report six patients who were found on newborn screening to have low citrulline and/or elevated C5-OH levels in whom confirmatory testing showed the combination of these two abnormal analytes. Mitochondrial sequencing revealed known pathogenic variants in MT-ATP6 at high heteroplasmy levels in all cases. MT-ATP6 at these heteroplasmy levels is associated with Leigh syndrome, a progressive neurodegenerative disease. Patients were treated with supplemental citrulline and, in some cases, mitochondrial cofactor therapy. These six patients have not experienced metabolic crises or developmental regression, and early diagnosis and management may help prevent the neurological sequelae of Leigh syndrome. The affected mothers and siblings are asymptomatic or paucisymptomatic (e.g. intellectual disability, depression, migraines, obsessive-compulsive disorder, and poor balance) despite high heteroplasmy or apparent homoplasmy of the familial variant, thus expanding the clinical spectrum seen in pathogenic variants of MT-ATP6. Confirmatory plasma amino acid analysis and acylcarnitine profiling should be ordered in a patient with either low citrulline and/or elevated C5-OH, as this combination appears specific for pathogenic variants in MT-ATP6.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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DOI：
10.1007/8904_2016_559
发表时间：
2017-01-01
期刊：
JIMD REPORTS, VOL 33
影响因子：
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作者：
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通讯作者：
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DOI：
10.1007/8904_2014_332
发表时间：
2014-01-01
期刊：
JIMD REPORTS, VOL 17
影响因子：
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作者：
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通讯作者：
Hickey, Scott