Hereditary optic neuropathies: autosomal dominant optic neuropathy with an OPA1 gene mutation and Leber hereditary optic neuropathy with a MT-ND4 gene mutation: case reports

Hereditary optic neuropathies are a genetically heterogeneous group of disorders leading to degeneration of retinal ganglion cells and the optic nerve. This group includes two main forms: autosomal dominant optic neuropathy and Leber hereditary optic neuropathy. The first one is caused by mutations in nuclear genes (such as OPA1). OPA1 mutations, which disrupt mitochondrial fusion, lead to their fragmentation and reduced energy production. This results in the death of retinal ganglion cells, which have high energy requirements. Their gradual death and degeneration of the optic nerve induce a gradual, symmetrical, and painless loss of vision starting in childhood (6–10 years). The incidence of the disorder is 1 in 35,000, with about 25% of patients maintaining high visual acuity. Leber hereditary optic neuropathy is a maternally inherited mitochondrial genetic disorder with a male predominance and an incidence of 1:27,000 to 1:45,000. The main cause of the disease is mitochondrial DNA mutations (m.3460G>A, m.11778G>A, and m.14484T>C), which disrupt the mitochondrial respiratory chain. The clinical presentation of this disorder is characterized by a subacute onset with rapid, painless bilateral loss of vision. There are asymptomatic, subacute (within 6 months of onset), dynamic (6–12 months), and chronic (greater than 12 months) disease stages. In recent years, recessive forms of hereditary optic neuropathy have been identified, associated with mutations in nuclear genes such as DNAJC30 and MCAT, which challenges the diagnosis. The presented article analyzes two clinical cases of autosomal dominant optic neuropathy and hereditary optic neuropathy. A comparative analysis of clinical and metabolic parameters, in particular blood lactate levels as a marker of mitochondrial dysfunction, revealed both differences and similarities between these disorders. This highlights the importance of a comprehensive approach, including a thorough clinical examination, molecular genetic testing, and assessment of the patient’s metabolic status. This comprehensive assessment is the key to early and accurate diagnosis, which enables personalized patient management and development of optimal treatment and rehabilitation strategies.