What do Ludwig van Beethoven and Pascal Couchepin, leader of the Swiss government, have in common? Music? Politics? Nope: hereditary hemochromatosis (HH). HH results in an overload of iron in the body, ultimately hindering the function of major organs. It is nothing special though – it happens to be the most common autosomal recessive disorder affecting approximately one out of three hundred individuals of North European descent.
The symptoms of HH have been known for decades but the culprit, which may well be at the heart of iron regulation, was only discovered in 1996. HFE is a protein whose 3D structure is very similar to that of a certain type of MHC molecule but, unlike the latter, has no apparent role in the immune system. This in itself was quite a discovery. HFE is lodged in cell membranes and binds both to transferrin receptor (TfR) and iron-loaded transferrin. Transferrin is also a protein which carts iron around the body and delivers it to various cells. Once transferrin and TfR are bound to HFE, the ternary complex enters the cell via endocytosis. The iron – now inside the cell – is consequently released and either used or stored.
Hereditary hemochromatosis is caused by a mutation in the HFE primary sequence which ultimately modifies the protein’s overall tertiary structure. As a result, HFE doesn’t appear at the cells’ surface and the body’s iron metabolism is disrupted. Consequently, iron accumulates – or decreases – where it shouldn’t, and major organs such as the heart, the pancreas and the liver function inadequately.
As for Beethoven, he had been suffering from abdominal pains since his early thirties and many thought that this was probably due to cirrhosis brought on by the exaggerated consumption of alcohol. Today though, some believe that the musician’s ill health may well be due to the combined effects of alcohol and HH. No one will ever know though; neither a histological examination nor hepatic iron concentration were done at the time.
So besides sharing popularity, albeit distant in time and pursuits, it could be that Beethoven and Pascal Couchepin also share a disease. However, one of them is definitely better off when it comes to diagnosis and treatment.