Which mutation in hematochromatosis cases does not correlate with increased iron accumulation?

In cases of hemochromatosis, mutations in the HFE gene are crucial for understanding iron metabolism and accumulation in the body. The C282Y mutation is widely recognized as the most significant genetic alteration that leads to increased iron absorption and overload in individuals. This mutation markedly affects the regulation of iron uptake in intestinal cells, resulting in excess iron accumulation.

In contrast, the H63D and S65T mutations are considered less impactful on iron accumulation. While they may be associated with some degree of altered iron metabolism, they do not cause the same severe iron accumulation seen with the C282Y mutation. Specifically, the H63D mutation is often seen in carriers who do not show significant iron overload compared to those with the C282Y mutation. The S65T mutation is even less common and does not have a well-established link to significant iron accumulation.

As such, when considering the H63D and S65T mutations together, it is clear that they do not correlate with increased iron accumulation to the same extent as the C282Y mutation does. This leads to the conclusion that both the H63D and S65T mutations, when assessed, do not significantly contribute to the pathological iron accumulation characteristic of hemochromatosis.