Based on the correlation of the disease characteristics and positions of the different pathological TOP3A variants on the crystal structure of TOP3A N-terminal domains, it has been proposed that variants with more severe effects on TOP3A catalytic activity could lead to Bloom syndrome-like disorder, while variants expected to have less severe impact on TOP3A catalytic activity could result in adult-onset mitochondrial disease [140]. Here, TOP3A is linked to inborn mitochondrial metabolism disorder.