RESUMO
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 EIF2B1-5 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 EIF2B 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 EIF2B4 and EIF2B5 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.
RESUMO
Se describen dos casos de enfermedad de Chagas en fase crónica, con mega deformaciones del tubo digestivo, ambos casos residentes del municipio de San Martín de Hidalgo, Jalisco. Con una evolución de 12 y 8 años respectivamente; el diagnóstico en ambos fue de acalasia de etiología desconocida. El primer paciente presenta megaesófago, megaduodeno y megaíleon (manifestaciones asociadas poco frecuentes). Los signos y síntomas digestivos fueron: disfagia, dolor retroesternal, regurgitación, sensación de plenitud gástrica, dolor epigástrico, vómito, sialorrea y pérdida de peso. El segundo paciente presenta disfagia, vómito regurgitación, tos de predominio nocturno, sialorrea, hipertrofia de parótidas y pérdida de peso. Los signos y síntomas comunes observadas en ambos casos son: disfagia, vómitos, regurgitación, sialorrea y pérdida de peso. Los signos y síntomas no comunes y asociados al padecimiento son: tos de predominio nocturno, hipertrofia de parótidas, dolor retroesternal, sensación de plenitud gástrica y dolor epigástrico.