Cholesterol is produced in a series of chemical reactions known as the Mevalonate Pathway. Each reaction follows on from the previous one. If one reaction or step cannot take place then the following reactions cannot take place. The diagram shows the steps in which each is catalysed or activated by an enzyme. For simplicity some steps have been omitted and they are represented by dashed lines. Notice that cholesterol, the dolichols, CoQ10 and other molecules can only be produced if every following chemical reaction takes place. Notice also that Vitamin D, the steroid hormones like testosterone, and the bile acids (necessary for the digestion of fats) cannot be produced without cholesterol.
Statins act near the top of the pathway, blocking the enzyme HMG-CoA reductase. Once this enzyme is blocked all the reactions coming after this step are blocked. So cholesterol is not produced and neither are other crucial chemicals like the dolichols and CoQ10. Furthermore, Vitamin D, bile acids and the steroid hormones are not produced. It is not surprising, then, that the side effects of statins are so horrendous.
In mevalonic aciduria, there is an inborn deficiency of the enzyme mevalonate kinase. Again the mevalonate pathway is disrupted and essential chemicals like cholesterol and CoQ10 are not produced. But that is not all. HMG-CoA reductase enables the conversion of HMG-CoA to mevalonic acid. In the absence of mevalonate kinase the mevalonic acid accumulates to toxic levels in both body tissues and fluids and is detectable in the urine, hence the name aciduria.
The disease is characterised by:
Treatment of this disease has not been successful. Cholesterol supplementation caused diarroea and fever. Equally unsuccessful has been supplementation with CoQ10.
In an effort to prevent the production of mevalonic acid, statin treatments have been tried. As explained above, statins block the enzyme HMG-CoA reductase so that mevalonic acid is not produced. The fever episodes became more frequent and more severe and blood levels of the enzyme creatine kinase increased. Note that raised creatine kinase levels also occur with rhabdomyolysis, one of the most severe side-effects of statin drugs. This shouldn't be surprising because statins have a similar mode of action to mevalonic aciduria.
Other treatments have been tried (such as steroids, anakinra usually used for rheumatoid arthritis) but without much success.