Iron Overload 2026 UPDATE

So first, Sam, how is iron stored?

Great question.

So the human body stores iron as ferritin and hemosiderin in the liver, spleen, marrow, duodenum, and skeletal muscle.

It also circulates bound to hemoglobin in our red blood cells and transferrin in the plasma.

There is no physiologic mechanism to actively excrete iron, so losses occur through desquamation of cells and, in premenopausal women, menstruation.

Iron hemostasis is regulated at the level of the absorption via hepatic hormone hepcidin.

And in iron overload, excessive storage iron accumulates in our organs, liver, heart, pancreas, endocrine organs, as well as macrophages.

And so what are some of the disorders in which we have iron overload?

Yep.

So those which, um, cause decreased hepcidin, so again, hepcidin deficiency can lead to hemochromatosis.

We think about HFE mutations, and that's Type 1.

This is the most common.

This is 95% of hereditary hemochromatosis.

There is the TFR2, which is transferrin receptor 2 mutations, and that's Type 3.

That's autosomal receptive.

There's the HJV, which is hemojuvelin mutations.

That's Type 2A, and that's juvenile hemochromatosis.

And there's HAMP, hepcidin mutations.

That's Type 2B, and that's juvenile hemochromatosis, which is extremely rare.

We also have ferroportin disease, which is Type 4, and that's mutations in the SLC40A1 or ferroportin gene.

This is autosomal dominant, unlike all the others, which are autosomal recessive.

So remember that one, the ferroportin disease.

This is dominant.

Everything else is recessive.

There's two major subtypes that are now recognized.