Mitochondriopathy caused by NTBI overload: the role of piracetam in the most problematic stage of H63D syndrome

This paper presents an in-depth discussion surrounding the potential implications of chronic non-transferrin bound iron (NTBI) overload, mitochondrial dysfunction, and the utilization of piracetam as a potential therapeutic approach in H63D syndrome. Starting from a patient scenario with iron overload secondary to a homozygous HFE gene H63D mutation and transferrin saturation constantly >50%, we explore the pathological mechanisms involving iron metabolism, oxidative stress, and cellular damage, with a particular focus on mitochondrial injury. The paper delves into the potentially complex interactions between iron, reactive oxygen species, and the mitochondrial respiratory chain, with an emphasis on how continued iron overload can lead to disease progression despite dietary interventions. It also speculates on the potential role of piracetam as a therapeutic option, discussing its possible mechanisms of action and considering the risk-benefit balance. Lastly, it underscores the complexity of iron overload conditions and the need for ongoing research into effective treatment strategies.