Sterol and Isoprenoid Research Consortium (STAIR)

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Mevalonate Kinase Deficiency (MKD)

What is Mevalonate Kinase Deficiency ?

Mevalonate Kinase Deficiency (MKD) is an autosomal recessive inherited disorder caused by deficiency of the enzyme mevalonate kinase (ATP: mevalonate 5-phosphotransferase) causing a defect in cholesterol biosynthesis. This deficiency result in two distinct types of disease: mevalonic aciduria (MVA), the severe form of MKD, and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), a milder form of MKD.

How many people have Mevalonate Kinase Deficiency ?

MKD is very rare. Approximately 30 individuals have been reported with MVA and more than 180 individuals have been reported with HIDS worldwide.

What causes Mevalonate Kinase Deficiency ?

MKD is caused by a mutation or change in the MVK gene. The MVK gene is responsible for producing an enzyme called mevalonate kinase. This enzyme plays an important role in converting mevalonic acid to cholesterol, other sterols and isoprenoids (all mevalonate derivatives), which are all involved in the normal functions of cells in our body. If the enzyme mevalonate kinase is unable to convert mevalonic acid to other chemicals the body needs, mevalonic acid will accumulate in body fluids and mevalonic acid derivatives will not be made. The lack of production of certain mevalonate derivatives is thought to cause the disease. The exact nature of these derivatives still needs to be characterized.

MKD is an inherited autosomal recessive disorder. Affected individuals inherit two copies of the mutated or changed MVK gene, one from each parent. Therefore the parents are “carriers” of MKD, meaning that they have one normal functioning copy and one non functioning copy of the gene. With each pregnancy, carriers of MKD have a 1 in 4 or 25% chance of having a child with MKD.

How is Mevalonate Kinase Deficiency diagnosed?

Individuals with MA will usually have elevated amount of mevalonic acid metabolites in the urine, blood, and cerebrospinal fluid. The initial diagnostic test is often a urine organic acid analysis. The diagnosis should be confirmed by measurement of enzyme activity and/or DNA mutation analysis. Those with HIDS often have normal mevalonic acid metabolites, especially between episodes, so that DNA mutation analysis is the diagnostic test of choice in that group, since IgD levels are not always elevated and enzyme activity measurement for this condition is not widely available and may not always distinguish HIDS from carriers or unaffected individuals.

What is/is there treatment for Mevalonate Kinase Deficiency ?

Treatment for MVA at this time should be considered supportive and investigational. There is one report of a child receiving a liver transplant followed by a hematopoietic stem cell transplant that seems to have shown improvement. Medications that modify the inflammatory response are increasingly being used for HIDS, but this use is off-label.