Mevalonate Kinase Deficiency (MKD) is a rare inherited condition characterized by recurrent fever and other symptoms although the affected individual presents no signs of infection of other related cause. This is considered as an auto inflammatory disorder where the unprovoked episodes of inflammation occur as the result of an abnormality of the innate immune system. Among the healthy individuals, the activation of the innate immune pathway happens as the result of tissue damage or a disease. The inflammation that occurs helps to fight off the disease. Among the MKD cases, these pathways are overactive causing the aggressive immune response when there isn’t an actual disease or tissue damage. MKD is not the same as the autoimmune disorders where the immune system mistakenly attacks the body’s healthy tissue.
Causes
MKD develops as the result of a mutation in the gene MVK which produces the enzyme known as mevalonate kinase. This enzyme is involved in the production of cholesterol and various substances that are important for cellular functions such as cell growth, cell maturation, gene activity, formation of cell’s structural framework and protein production. The genetic mutation results in the deficiency of mevalonate kinase enzyme activity. Research suggests that the symptoms of this condition develop as the result of an accumulation of mevalonic acid or the shortage of the substances produced from mevalonic acid. MKD is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. The parents of the affected individual do not necessarily exhibit the symptoms associated with this condition.
Symptoms
The symptoms can range from mild to severe condition including life-threatening complications. The mild form of this condition is characterized by the recurrent episodes of fever with no associated infection. These episodes can include abdominal pain, swelling of the lymph nodes, joint inflammation, pain, abnormal enlargement of the liver, ulcers in the mouth, diarrhea and fatigue. Some of the individuals can have episodes that last for three to seven days with varying frequency. The episodes can be frequent among children than the adults. Less common symptoms include inflammation of the conjunctiva, kidney problems, pneumococcal infection, inflammation of the lining of the colon (colitis), dehydration, diarrhea and bloody stools.
Diagnosis
The diagnosis of MKD is based on the clinical evaluation, the identification of features associated with this condition and various tests. The increased level of immunoglobulin D in the blood can be an indication of MKD but does not confirm the diagnosis as some individuals may present normal levels. A urine sample can also detect the high levels of mevalonate acid which is also an indication and not a confirmation of the diagnosis. MKD can be confirmed with the molecular genetic testing that seeks to identify the gene that is responsible for causing this condition.
Treatment
The treatment is based on the symptoms that are evident in each case. Individuals who have mild symptoms and few episodes, the treatment can include paracetamol, corticosteroids and nonsteroidal anti-inflammatories which can cause the complete or partial remission during the fever. Some of the affected individuals have been treated with anakinra which is an interleukin-receptor antagonist that blocks the activity of interleukin-1. Other individuals have been treated with medications that block the activity of tumor necrosis factor that is involved in inflammation and the use of the immunosuppressive drug.
References
https://rarediseases.org/rare-diseases/hyper-igd-syndrome/
https://ghr.nlm.nih.gov/condition/mevalonate-kinase-deficiency#inheritance
http://autoinflammatory.org/hids.php
https://www.ucl.ac.uk/amyloidosis/pdfs/mkd
