Escobar-Pacheco Mariana, Luna-Álvarez Mariana, Dávila-Ortiz de Montellano David, Yescas-Gómez Petra, Ramírez-García Miguel Á
Genetics, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, MEX.
Genetics, National Institute of Pediatrics, Mexico City, MEX.
Cureus. 2024 Jul 13;16(7):e64497. doi: 10.7759/cureus.64497. eCollection 2024 Jul.
Leukodystrophies comprise a spectrum of genetic disorders affecting white matter (WM) formation in the central nervous system (CNS), of which vanishing white matter disease (VWMD) is one. VWMD presents with progressive neurological deterioration and a variety of manifestations. Ovarioleukodystrophy, a subtype of VWMD, exhibits a distinctive clinical profile encompassing both CNS WM alterations and ovarian dysfunction. Variants in genes of the eukaryotic translation initiation factor 2B (EIF2B) complex affect the full form and are implicated in VWMD, including ovarioleukodystrophy. This work aimed to systematically review all published cases of ovarioleukodystrophy associated with variants in the gene complex based on the first case identified in a Mexican population. We performed a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines of published cases of ovarioleukodystrophy associated with the gene complex, including a newly identified case from Mexico. We identified 207 publications using PUBMED, SCOPUS, and PMC databases. One hundred fifty-one publications were eliminated due to duplicates, titles, abstracts, or other reasons, while 56 publications were revised, of which 29 were eliminated because they dealt with other genes or non-human research, and 27 reports were assessed for eligibility. Finally, 14 reports describing ovarian involvement, neuroimaging, and molecular variants were included. Our review identified 20 cases worldwide, with a median age of onset of 19 years. Clinical features included WM involvement, ovarian abnormalities, gait disturbances, epilepsy, cognitive and language impairment, and other neurological manifestations. Neuroimaging showed characteristic WM changes, highlighting the importance of MRI in diagnosis. Missense variants predominated among the identified genetic mutations, especially in the and genes. Ovarioleukodystrophy is an ultra-rare disorder with a wide range of clinical manifestations and ovarian changes. Gynecological evaluation is crucial in suspected cases of ovarioleukodystrophy, as ovarian manifestations may precede neurological symptoms. The role of MRI is crucial in the diagnostic approach to this entity. Continued collaborative efforts are essential to elucidate genotype-phenotype correlations, improve clinical management, and promote therapeutic advances for this rare disorder.
脑白质营养不良包括一系列影响中枢神经系统（CNS）白质（WM）形成的遗传性疾病，其中消失性白质病（VWMD）是其中之一。VWMD表现为进行性神经功能恶化和多种临床表现。卵巢脑白质营养不良是VWMD的一种亚型，具有独特的临床特征，包括CNS白质改变和卵巢功能障碍。真核生物翻译起始因子2B（EIF2B）复合体基因的变异影响其完整形式，并与VWMD有关，包括卵巢脑白质营养不良。这项工作旨在基于在墨西哥人群中发现的首例病例，系统回顾所有已发表的与该基因复合体变异相关的卵巢脑白质营养不良病例。我们根据系统评价和Meta分析的首选报告项目（PRISMA）指南，对已发表的与该基因复合体相关的卵巢脑白质营养不良病例进行了系统回顾，包括一个来自墨西哥的新确诊病例。我们使用PUBMED、SCOPUS和PMC数据库识别了207篇出版物。151篇出版物因重复、标题、摘要或其他原因被排除，56篇出版物被修订，其中29篇因涉及其他基因或非人类研究而被排除，27份报告被评估是否符合纳入标准。最后，纳入了14份描述卵巢受累、神经影像学和分子变异的报告。我们的综述在全球范围内确定了20例病例，发病年龄中位数为19岁。临床特征包括白质受累、卵巢异常、步态障碍、癫痫、认知和语言障碍以及其他神经学表现。神经影像学显示出特征性的白质变化，突出了MRI在诊断中的重要性。在已识别的基因突变中，错义变异占主导，尤其是在[具体基因1]和[具体基因2]基因中。卵巢脑白质营养不良是一种极其罕见的疾病，具有广泛的临床表现和卵巢变化。在疑似卵巢脑白质营养不良的病例中，妇科评估至关重要，因为卵巢表现可能先于神经症状出现。MRI在该疾病的诊断方法中起着关键作用。持续的合作努力对于阐明基因型-表型相关性、改善临床管理以及推动这种罕见疾病的治疗进展至关重要。
