Mevalonate Kinase Deficiency (MKD), also known as Hyperimmunoglobulin D syndrome and periodic fever syndrome (HIDS)

A patient with MKD, during an attack

A patient with MKD, during an attack

MKD is an extremely rare, autosomal recessive condition. It was first described in Dutch children in 1984 and is most common in North West Europe, especially in the Netherlands. This syndrome is due to mutations in the MVK gene which encodes an enzyme called mevalonate kinase. Affected children usually develop recurrent attacks of fever in their first year of life, each typically lasting 3 to 7 days. These are often accompanied by headache, enlarged lymph nodes (glands) in the neck, joint pains, diarrhoea, vomiting and rash. Attacks often occur within hours of immunizations or minor infections, trauma, surgery or stress. The disease may get milder in adolescence.

There are often high levels of types of antibody called IgD and IgA, as well as the raised levels of all the inflammatory markers seen in all the inherited fever syndromes. Diagnosis rests on suspicious clinical findings and identification of mutations in both MVK genes on genetic testing.

Treatment of MKD involves avoiding immunizations as these are well known to precipitate attacks. Drug treatment is difficult although there is now evidence that injected drugs, such as anakinra, that block certain inflammatory proteins (cytokines) may be effective. Anakinra has to be given at home every day. Another drug of this type, etanercept, may also be helpful.

The side effects of these drugs include:

  • stinging
  • skin redness at the injection site, in some people
  • increased risk of infection.

In general the infections reported have been mild but all patients should be screened for tuberculosis and asked about a history of other infections before starting such drugs.

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