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 can lead to one of two ends of a clinical spectrum: mevalonic aciduria (MVA), the severe form of MKD, and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) a more benign form of MKD.
Mevalonic aciduria is characterized by delayed physical and mental development (intellectual disability), failure to thrive, recurrent episodes of fever with vomiting and diarrhea, enlarged liver, spleen and lymph nodes, microcephaly (small head size), cataract, low muscle tone, short stature, distinct facial features, ataxia (abnormal movements), and anemia.
HIDS is characterized by recurrent episodes of fever associated with swollen lymph nodes, joint pain, gastrointestinal issues and skin rash.
How many people have Mevalonate Kinase Deficiency ?
MKD is very rare. Approximately 30 patients have been reported with MVA and more than 180 patients 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 need 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 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, since IgD levels are not always elevated.
What is/is there treatment for Mevalonate Kinase Deficiency ?
There has been no successful treatment for MVA. Dietary supplementation of cholesterol may reduce the frequency and severity of fever in some of the mildly affected patients. Corticosteroids are sometimes useful in treating fever episodes. Inhibitors of inflammatory mediators are increasingly being used.