PDF(Pubmed)
Abstract：
BACKGROUND: Glutaric aciduria type II (GA2) is a rare genetic disorder inherited in an autosomal recessive manner. Double dosage mutations in GA2 corresponding genes, ETFDH, ETFA, and ETFB, lead to defects in the catabolism of fatty acids, and amino acids lead to broad-spectrum phenotypes, including muscle weakness, developmental delay, and seizures. product of these three genes have crucial role in transferring electrons to the electron transport chain (ETC), but are not directly involve in ETC complexes.
METHODS: Here, by using exome sequencing, the cause of periodic cryptic gastrointestinal complications in a 19-year-old girl was resolved after years of diagnostic odyssey. Protein modeling for the novel variant served as another line of validation for it.
RESULTS: Exome Sequencing (ES) identified two variants in ETFDH: ETFDH:c.926T>G and ETFDH:c.1141G>C. These variants are likely contributing to the crisis in this case. To the best of our knowledge at the time of writing this manuscript, variant ETFDH:c.926T>G is reported here for the first time. Clinical manifestations of the case and pathological analysis are in consistent with molecular findings. Protein modeling provided another line of evidence proving the pathogenicity of the novel variant. ETFDH:c.926T>G is reported here for the first time in relation to the causation GA2.
CONCLUSIONS: Given the milder symptoms in this case, a review of GA2 cases caused by compound heterozygous mutations was conducted, highlighting the range of symptoms observed in these patients, from mild fatigue to more severe outcomes. The results underscore the importance of comprehensive genetic analysis in elucidating the spectrum of clinical presentations in GA2 and guiding personalized treatment strategies.
METHODS: Here, by using exome sequencing, the cause of periodic cryptic gastrointestinal complications in a 19-year-old girl was resolved after years of diagnostic odyssey. Protein modeling for the novel variant served as another line of validation for it.
RESULTS: Exome Sequencing (ES) identified two variants in ETFDH: ETFDH:c.926T>G and ETFDH:c.1141G>C. These variants are likely contributing to the crisis in this case. To the best of our knowledge at the time of writing this manuscript, variant ETFDH:c.926T>G is reported here for the first time. Clinical manifestations of the case and pathological analysis are in consistent with molecular findings. Protein modeling provided another line of evidence proving the pathogenicity of the novel variant. ETFDH:c.926T>G is reported here for the first time in relation to the causation GA2.
CONCLUSIONS: Given the milder symptoms in this case, a review of GA2 cases caused by compound heterozygous mutations was conducted, highlighting the range of symptoms observed in these patients, from mild fatigue to more severe outcomes. The results underscore the importance of comprehensive genetic analysis in elucidating the spectrum of clinical presentations in GA2 and guiding personalized treatment strategies.
摘要：
背景：II型戊二酸尿症（GA2）是一种罕见的常染色体隐性遗传的遗传性疾病。GA2相应基因的双剂量突变，EFDH,ETFA,和ETFB，导致脂肪酸分解代谢的缺陷，和氨基酸导致广谱表型，包括肌肉无力,发育迟缓,和癫痫发作。这三个基因的产物在将电子转移到电子传递链（ETC）中具有至关重要的作用，但不直接参与ETC复合物。
方法：这里，通过使用外显子组测序，一个19岁女孩的周期性隐匿性胃肠道并发症的原因在经过多年的诊断试验后得到解决。新变体的蛋白质建模作为其另一个验证线。
结果：外显子组测序（ES）在ETFDH中鉴定出两种变体：ETFDH：c.926T>G和ETFDH：c.1141G>C。在这种情况下，这些变体可能会导致危机。据我们所知，在写这篇手稿的时候，变体ETFDH：c.926T>G是首次报道。病例的临床表现和病理分析与分子检查结果一致。蛋白质模型提供了另一个证据线证明新变体的致病性。ETFDH：c.926T>G在此首次报告与因果关系GA2有关。
结论：鉴于这种情况下症状较轻，对复合杂合子突变引起的GA2病例进行了回顾，突出这些患者的症状范围，从轻度疲劳到更严重的结果。结果强调了综合遗传分析在阐明GA2临床表现谱和指导个性化治疗策略方面的重要性。
方法：这里，通过使用外显子组测序，一个19岁女孩的周期性隐匿性胃肠道并发症的原因在经过多年的诊断试验后得到解决。新变体的蛋白质建模作为其另一个验证线。
结果：外显子组测序（ES）在ETFDH中鉴定出两种变体：ETFDH：c.926T>G和ETFDH：c.1141G>C。在这种情况下，这些变体可能会导致危机。据我们所知，在写这篇手稿的时候，变体ETFDH：c.926T>G是首次报道。病例的临床表现和病理分析与分子检查结果一致。蛋白质模型提供了另一个证据线证明新变体的致病性。ETFDH：c.926T>G在此首次报告与因果关系GA2有关。
结论：鉴于这种情况下症状较轻，对复合杂合子突变引起的GA2病例进行了回顾，突出这些患者的症状范围，从轻度疲劳到更严重的结果。结果强调了综合遗传分析在阐明GA2临床表现谱和指导个性化治疗策略方面的重要性。
