Abstract：
BACKGROUND: Pathogenic variants in the NDUFV1 gene disrupt mitochondrial complex I, leading to neuroregression with leukoencephalopathy and basal ganglia involvement on neuroimaging. This study aims to provide a concise review on NDUFV1-related disorders while adding the largest cohort from a single center to the existing literature.
METHODS: We retrospectively collected genetically proven cases of NDUFV1 pathogenic variants from our center over the last decade and explored reported instances in existing literature. Magnetic resonance imaging (MRI) patterns observed in these patients were split into three types-Leigh (putamen, basal ganglia, thalamus, and brainstem involvement), mitochondrial leukodystrophy (ML) (cerebral white matter involvement with cystic cavitations), and mixed (both).
RESULTS: Analysis included 44 children (seven from our center and 37 from literature). The most prevalent comorbidities were hypertonia, ocular abnormalities, feeding issues, and hypotonia at onset. Children with the Leigh-type MRI pattern exhibited significantly higher rates of breathing difficulties, whereas those with a mixed phenotype had a higher prevalence of dystonia. The c.1156C>T variant in exon 8 of the NDUFV1 gene was the most common variant among individuals of Asian ethnicity and is predominantly associated with irritability and dystonia. Seizures and Leigh pattern of MRI of the brain was found to be less commonly associated with this variant. Higher rate of mortality was observed in children with Leigh-type pattern on brain MRI and those who did not receive mitochondrial cocktail.
CONCLUSIONS: MRI phenotyping might help predict outcome. Appropriate and timely treatment with mitochondrial cocktail may reduce the probability of death and may positively impact the long-term outcomes, regardless of the genetic variant or age of onset.
METHODS: We retrospectively collected genetically proven cases of NDUFV1 pathogenic variants from our center over the last decade and explored reported instances in existing literature. Magnetic resonance imaging (MRI) patterns observed in these patients were split into three types-Leigh (putamen, basal ganglia, thalamus, and brainstem involvement), mitochondrial leukodystrophy (ML) (cerebral white matter involvement with cystic cavitations), and mixed (both).
RESULTS: Analysis included 44 children (seven from our center and 37 from literature). The most prevalent comorbidities were hypertonia, ocular abnormalities, feeding issues, and hypotonia at onset. Children with the Leigh-type MRI pattern exhibited significantly higher rates of breathing difficulties, whereas those with a mixed phenotype had a higher prevalence of dystonia. The c.1156C>T variant in exon 8 of the NDUFV1 gene was the most common variant among individuals of Asian ethnicity and is predominantly associated with irritability and dystonia. Seizures and Leigh pattern of MRI of the brain was found to be less commonly associated with this variant. Higher rate of mortality was observed in children with Leigh-type pattern on brain MRI and those who did not receive mitochondrial cocktail.
CONCLUSIONS: MRI phenotyping might help predict outcome. Appropriate and timely treatment with mitochondrial cocktail may reduce the probability of death and may positively impact the long-term outcomes, regardless of the genetic variant or age of onset.
摘要：
背景：NDUFV1基因的致病变异破坏线粒体复合物I，导致神经退化与脑白质病变和基底神经节参与神经影像学。本研究旨在对NDUFV1相关疾病进行简要综述，同时将单个中心的最大队列添加到现有文献中。
方法：我们回顾性地收集了过去十年来我们中心经遗传证实的NDUFV1致病变种的病例，并探讨了现有文献中报道的实例。在这些患者中观察到的磁共振成像（MRI）模式分为三种类型-Leigh（壳核，基底神经节,丘脑,和脑干参与)，线粒体脑白质营养不良（ML）（脑白质累及囊性空洞），混合（两者）。
结果：分析包括44名儿童（7名来自我们中心，37名来自文献）。最普遍的合并症是高张力症，眼部异常，喂养问题，和起病时的张力减退。Leigh型MRI表现出明显更高的呼吸困难率，而具有混合表型的患者的肌张力障碍患病率较高。NDUFV1基因第8外显子的c.1156C>T变异是亚洲种族个体中最常见的变异，主要与易怒和肌张力障碍有关。发现大脑MRI的癫痫发作和Leigh模式与这种变异不太相关。在脑MRI上具有Leigh型模式的儿童和未接受线粒体鸡尾酒的儿童中观察到更高的死亡率。
结论：MRI表型可能有助于预测结果。适当和及时的线粒体鸡尾酒治疗可能会降低死亡的可能性，并可能对长期结果产生积极影响。无论遗传变异或发病年龄。
方法：我们回顾性地收集了过去十年来我们中心经遗传证实的NDUFV1致病变种的病例，并探讨了现有文献中报道的实例。在这些患者中观察到的磁共振成像（MRI）模式分为三种类型-Leigh（壳核，基底神经节,丘脑,和脑干参与)，线粒体脑白质营养不良（ML）（脑白质累及囊性空洞），混合（两者）。
结果：分析包括44名儿童（7名来自我们中心，37名来自文献）。最普遍的合并症是高张力症，眼部异常，喂养问题，和起病时的张力减退。Leigh型MRI表现出明显更高的呼吸困难率，而具有混合表型的患者的肌张力障碍患病率较高。NDUFV1基因第8外显子的c.1156C>T变异是亚洲种族个体中最常见的变异，主要与易怒和肌张力障碍有关。发现大脑MRI的癫痫发作和Leigh模式与这种变异不太相关。在脑MRI上具有Leigh型模式的儿童和未接受线粒体鸡尾酒的儿童中观察到更高的死亡率。
结论：MRI表型可能有助于预测结果。适当和及时的线粒体鸡尾酒治疗可能会降低死亡的可能性，并可能对长期结果产生积极影响。无论遗传变异或发病年龄。
