A rare de novo mutation, m.1630A>G, in the mitochondrial tRNAVal (MT-TV) gene in a child with epilepsy: case report and review of the literature.

Abstract

Background: Mitochondrial diseases represent a diverse group of disorders caused by defects in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), leading to a wide range of clinical manifestations. These diseases can affect multiple organs, particularly the nervous system, and present with symptoms such as epilepsy, neurodevelopmental delays, and muscular disorders. Over 300 genetic mutations have been linked to these conditions, with clinical heterogeneity being a hallmark of mitochondrial diseases. Early diagnosis and management are crucial, especially in pediatric cases where the disease burden may evolve with age. The aim of this study is to explore the variability in clinical presentation and progression associated with specific genetic mutations, using the case of a rare de novo mutation in the MT-TV gene as an illustrative example, and to discuss the implications for clinical diagnosis.

Case description: This paper reports on a rare de novo mutation, m.1630A>G, in the MT-TV gene of a 3-year-old boy with epilepsy. In contrast to previously reported cases of the mitochondrial neurogastrointestinal encephalopathy (MNGIE)-like disease/the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) associated with the m.1630A>G mutation, this patient exhibited an earlier age of onset, simpler clinical manifestations, and lower heterogeneity levels in the blood.

Conclusions: This case offers significant insights into the intricate nature of mitochondrial diseases, especially in pediatric populations. It highlights the critical importance of regular physical examinations and vigilant monitoring for potential multi-system involvement, which are essential for early detection and timely symptomatic intervention to mitigate further damage. Furthermore, this case underscores the necessity to investigate factors influencing clinical penetrance, such as the interplay between mitochondrial and nuclear gene mutations, heterogeneity levels, and age-related accumulation of cellular damage, to better understand disease progression and optimize therapeutic strategies.