Leber hereditary optic neuropathy: A case report of concurrent rare mitochondrial mutations and ABCA4 nuclear gene mutation

Purpose: This case report aims to describe the clinical presentation of a 21-year-old male patient with subacute bilateral painless vision loss, clinically consistent with Leber hereditary optic neuropathy (LHON), a mitochondrially inherited disorder and to investigate the genetic mutations associated with this condition. Methods: Genetic testing was performed on the patient to identify potential LHON-related mutations. Additionally, the patient's medical history and clinical examination findings were recorded. Results: The patient tested negative for the three most common LHON-related mutations but exhibited two homoplasmic mitochondrial mutations with unclear significance, m3461 C>T (MT-ND1) and m9358 C>T (MT_CO3). Furthermore, two pathogenic variants of ABCA4 (c.3322>T and c.4539+2028 C>T) were identified in the patient's genetic profile. Discussion/conclusion: This case underscores the complex interplay between mitochondrial and nuclear mutations in the pathophysiology of LHON. Despite the absence of common LHON mutations, the presence of these mitochondrial and nuclear mutations likely contributed to the patient's LHON phenotype. This case also highlights the importance of considering environmental factors and genetic interactions in LHON development.