MNGIE(线粒体神经胃肠脑肌病)是一种超罕见的常染色体隐性遗传疾病,可导致编码胸苷磷酸化酶的核基因突变。症状包括胃肠动力障碍,恶病质,上睑下垂,眼外肌麻痹,感觉运动神经病和无症状的白质脑病。我们描述了第一例MNGIE伴脑膜脑炎的病例,该病例最终导致了家族性诊断,结束了诊断性疾病。我们回顾性审查了电子病历,并发送了索引病例及其家庭成员的整个外显子组测序。我们报告了所有受影响的兄弟姐妹中TYMP基因中发现的变异c.877T>Cp。(Cys293Arg)显示出与MNGIE相关的典型临床表现。据我们所知,这在文献中以及人群数据库dbSNP(单核苷酸多态性数据库)和gnomAD(基因组聚集数据库)中都没有描述.此外,它位于高度保守的残留物中,生物信息学分析表明它很可能是有害的。此外,我们在1983-2023年的3个数据库的文献中进行了广泛检索后,估计了550例MNGIE病例(包括本研究中的5例).此外,我们在TYMP以外的基因中鉴定出44例具有MNGIE样表型的患者.MNGIE样表型影响POLG1、RRM2B、LIG3、RRM1、MTTV1和MT-RNR1基因。
一种罕见的神经系统表现在多年没有诊断后揭开了一个家庭的医学奥秘:MNGIE是一种罕见的疾病,由一种基因的变化引起,这种基因导致胸苷磷酸化酶缺乏。患者抱怨体重明显下降,四肢刺痛和麻木,肌肉无力,消化问题和眼睑下垂。我们遇到了一个病人的症状和体征的炎症和它的保护衬里。然而,实验室测试没有结果,而他的病情不断恶化。遗传分析揭示了以前文献中未描述的新突变。在多年没有收到关于他们症状的答案之后,这也有助于诊断整个家庭。我们还在1983年至2023年的科学文献中发现了550例MNGIE。这个案例强调了采取家庭的整个家族史和基因检测来解决复杂的医疗案件的重要性。
MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) is an ultra-rare autosomal recessive disorder that leads to mutations in the nuclear genes encoding thymidine phosphorylase. Symptoms include gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy and asymptomatic leukoencephalopathy. We describe the first case of MNGIE with meningoencephalitis that ultimately led to a familial diagnosis ending a diagnostic odyssey. We retrospectively reviewed the electronic medical records and sent whole exome sequencing for the index case and his family members. We report the variant c.877T>C p.(Cys293Arg) found in TYMP gene in all affected siblings showed typical clinical manifestations related to MNGIE. To the best of our knowledge, this is not described in the literature nor in the population databases dbSNP (Single Nucleotide Polymorphism Database) and gnomAD (Genome Aggregation Database). Additionally, it is located in a highly conserved residue and the bioinformatic analysis suggests it is most probably deleterious. Moreover, we estimated 550 number of cases of MNGIE (including 5 cases in this study) after performing an extensive search in the literature across 3 databases from 1983-2023. In addition, we identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.
A rare neurological presentation unravels a family’s medical mystery after years of no diagnosis: MNGIE is a rare disease caused by changes in a gene that cause deficiency in an enzyme called thymidine phosphorylase. Patients complain of significant weight loss, tingling and numbness in their extremities, muscle weakness, digestive issues and drooping eyelids. We encountered a patient with symptoms and signs of inflammation of the brain and it\'s protective lining. However, laboratory tests were inconclusive whilst his condition kept deteriorating. A genetic analysis revealed a new mutation not described in the literature before. This has also helped to diagnose the entire family after years of not receiving an answer regarding their symptoms. We also found 550 cases of MNGIE published in the scientific literature from 1983 to 2023. This case highlights the importance of taking a family’s entire family history and genetic testing to solve complex medical cases.