病例报告:MT-ATP6基因m.8993T>G致病性变异引起Leigh综合征的异常神经学特征

IF 1.7 4区 生物学 Q3 GENETICS & HEREDITY
Ramya Treitel, Julie McLaughlin, Marta Frigeni
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引用次数: 0

摘要

MT-ATP6基因m.8993T>G致病性变异与Leigh综合征有关,特别是在表现出高度异质性的患者中。虽然患者可能表现出广泛的表型谱,但特征性表现包括脑MRI上基底节区和脑干的双侧对称高信号,特别是在t2加权和液体衰减反转恢复序列上。此外,与这种致病变异相关的生化表型通常类似于多种羧化酶缺乏和近端尿素循环障碍。本报告描述了一个男性婴儿与非典型的神经系统表现的利综合征。在2个月大时,他出现了左颞起源的癫痫持续状态,难以治疗。最初的脑部MRI显示左侧颞叶有一大片非增强信号异常,引起对感染性病因的关注。然而,生化检测显示低硝酸钠血症、3-羟基异戊基肉碱升高、丙酰肉碱升高、尿中乳酸和丙酮酸排泄,提示进一步研究MT-ATP6线粒体疾病。线粒体DNA分析证实在MT-ATP6基因中存在m.8993T>G同源致病变异。尽管给予瓜氨酸和大剂量生物素治疗,患者仍在5周后死于严重呼吸道感染后的心肺衰竭。对他的新生儿筛查进行回顾性检查,发现两项筛查显示瓜氨酸含量低,最终在第三次筛查中被清除,延误了诊断。本病例强调了考虑MT-ATP6线粒体疾病在非典型神经症状和生化异常患者鉴别诊断中的重要性。它还强调了新生儿筛查在识别潜在线粒体疾病方面的价值,早期诊断和及时干预可以改善结果,即使在严重的情况下也是如此。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Case Report: Unusual Neurological Features of Leigh Syndrome due to m.8993T>G Pathogenic Variant in the MT-ATP6 Gene.

The MT-ATP6 gene m.8993T>G pathogenic variant has been associated with Leigh syndrome, especially in patients exhibiting a high degree of heteroplasmy. Although patients may present with a wide phenotypic spectrum, characteristic findings include bilateral, symmetric hyperintensities in the basal ganglia and brainstem on brain MRI, particularly on T2-weighted and fluid-attenuated inversion recovery sequences. Additionally, the biochemical phenotype associated with this pathogenic variant often mimics that of multiple carboxylase deficiency and proximal urea cycle disorders. This report describes a male infant with an atypical neurological presentation of Leigh syndrome. At 2 months of age, he presented with status epilepticus of left temporal origin that was refractory to treatment. Initial brain MRI revealed a large region of non-enhancing signal abnormality in the left temporal lobe, raising concern for an infectious etiology. However, biochemical testing revealed hypocitrullinemia, elevated 3-hydroxyisovalerylcarnitine, elevated propionylcarnitine, and urinary excretion of lactate and pyruvate, prompting further investigation for MT-ATP6 mitochondrial disease. Mitochondrial DNA analysis confirmed the presence of a homoplasmic m.8993T>G pathogenic variant in the MT-ATP6 gene. Despite treatment with citrulline and high-dose biotin, the patient died 5 weeks later due to cardiorespiratory failure following a severe respiratory infection. Retrospective review of his newborn screening revealed two screens positive for low citrulline that were ultimately cleared on a third screen, delaying the diagnosis. This case underscores the importance of considering MT-ATP6 mitochondrial disease in the differential diagnosis of patients presenting with atypical neurological symptoms and biochemical abnormalities. It also highlights the value of newborn screening in identifying potential mitochondrial disorders, where early diagnosis and timely intervention may improve outcomes, even in severe cases.

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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
432
审稿时长
2-4 weeks
期刊介绍: The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts: Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .
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