What are the genetic changes related to mevalonate kinase deficiency ?
Mutations in the MVK gene cause mevalonate kinase deficiency. The MVK gene provides instructions for making the mevalonate kinase enzyme. This enzyme is involved in the production of cholesterol, which is later converted into steroid hormones and bile acids. Steroid hormones are needed for normal development and reproduction, and bile acids are used to digest fats. Mevalonate kinase also helps to produce other substances that are necessary for certain cellular functions, such as cell growth, cell maturation (differentiation), formation of the cell's structural framework (the cytoskeleton), gene activity (expression), and protein production and modification.  Most MVK gene mutations that cause mevalonate kinase deficiency result in an enzyme that is unstable and folded into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have normal production of cholesterol, steroid hormones, and bile acids.  It is unclear how a lack of mevalonate kinase activity causes the signs and symptoms of this condition. Some researchers believe the features may be due to a buildup of mevalonic acid, the substance that mevalonate kinase normally acts on. Other researchers think that a shortage of the substances produced from mevalonic acid, such as those substances necessary for certain cellular functions, causes the fever episodes and other features of this condition.  The severity of the enzyme deficiency determines the severity of the condition. People who have approximately 1 to 20 percent of normal mevalonate kinase activity typically develop HIDS. Individuals who have less than 1 percent of normal enzyme activity usually develop MVA.