Sereikaite Liveta, Vilkeviciute Alvita, Glebauskiene Brigita, Traberg Rasa, Gelzinis Arvydas, Piskiniene Raimonda, Zemaitiene Reda, Ugenskiene Rasa, Liutkeviciene Rasa
Department of Ophthalmology, Lithuanian University of Health Sciences, Eiveniu Str. 2, LT-50161 Kaunas, Lithuania.
Laboratory of Ophthalmology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu Str. 2, LT-50161 Kaunas, Lithuania.
Genes (Basel). 2025 Aug 23;16(9):993. doi: 10.3390/genes16090993.
Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case of arLHON in a patient of Lithuanian descent and confirms the DnaJ Heat Shock Protein Family (Hsp40) Member C30 () c.152A>G p.(Tyr51Cys) founder variant.
A 34-year-old Lithuanian man complained of headache and sudden, painless loss of central vision in his right eye. On examination, the visual acuity of the right and left eyes was 0.1 and 1.0, respectively. Visual-field examination revealed a central scotoma in the right eye, and visual evoked potentials (VEPs) showed prolonged latency in both eyes. Optical coherence tomography showed thickening of the retinal nerve fiber layer in the upper quadrant of the optic disk in the left eye. Magnetic resonance imaging of the head showed evidence of optic nerve inflammation in the right eye. Blood tests were within normal range and showed no signs of inflammation. Retrobulbar neuritis of the right eye was suspected, and the patient was treated with steroids, which did not improve visual acuity. He later developed visual loss in the left eye as well. A genetic origin of the optic neuropathy was suspected, and a complete mitochondrial DNA analysis was performed, but it did not reveal any pathologic mutations. Over time, the visual acuity of both eyes slowly deteriorated, and the retinal nerve fiber layer (RNFL) thinning of the optic disks progressed. A multidisciplinary team of specialists concluded that vasculitis or infectious disease was unlikely to be the cause of the vision loss, and a genetic cause for the disease was still suspected, although a first-stage genetic test did not yield the diagnosis. Thirty-three months after disease onset, whole-exome sequencing revealed a pathogenic variant in the gene, leading to the diagnosis of arLHON. Treatment with Idebenone was started 35 months after the onset of the disease, resulting in no significant worsening of the patient's condition.
This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians.
Leber遗传性视神经病变（LHON）是最常见的线粒体疾病和一种遗传性视神经病变。最近，发现了两种不同的LHON遗传类型：线粒体遗传LHON（mtLHON）和常染色体隐性遗传LHON（arLHON）。我们的病例报告是首例确诊的立陶宛裔arLHON患者，并证实了DnaJ热休克蛋白家族（Hsp40）成员C30（）c.152A>G p.（Tyr51Cys）始祖变异。
一名34岁的立陶宛男子主诉头痛，右眼突然无痛性中心视力丧失。检查发现，右眼和左眼的视力分别为0.1和1.0。视野检查显示右眼有中心暗点，视觉诱发电位（VEP）显示双眼潜伏期延长。光学相干断层扫描显示左眼视盘上象限视网膜神经纤维层增厚。头部磁共振成像显示右眼有视神经炎症迹象。血液检查在正常范围内，未显示炎症迹象。怀疑右眼为球后视神经炎，患者接受了类固醇治疗，但视力未改善。后来他的左眼也出现了视力丧失。怀疑视神经病变有遗传起源，进行了完整的线粒体DNA分析，但未发现任何病理性突变。随着时间的推移，双眼视力逐渐恶化，视盘的视网膜神经纤维层（RNFL）变薄进展。一个多学科专家团队得出结论，血管炎或传染病不太可能是视力丧失的原因，尽管一期基因检测未得出诊断，但仍怀疑该病有遗传原因。发病33个月后，全外显子测序在该基因中发现了一个致病变异，从而确诊为arLHON。发病35个月后开始使用艾地苯醌治疗，患者病情未出现明显恶化。
本病例强调了将arLHON作为视神经病变患者可能诊断的重要性，因为arLHON的表型似乎与mtLHON相同，临床医生无法区分。
