Mevalonate kinase deficiency (MKD) and its milder spectrum hyper IgD syndrome (HIDS) is a rare monogenic disease with multiple organ manifestations. HIDS patients most commonly present with recurrent febrile attacks, gastrointestinal symptoms (abdominal pain, nausea, and vomiting), inflammatory arthritis, and arthralgia as well as mucocutaneous manifestations. Disease usually manifests in childhood, although adult cases of HIDS have been described in literature.
The most common mutation in MKD is pV377I (G1129A) and is primarily observed among heterozygous individuals with HIDS. Other genetic mutations have also been described in literature, but not all of them seem to correlate with clinical manifestations.
Increased levels of immunoglobulin D (IgD) as well as high levels of IL-1, IL-6, and tumor necrosis factor-α (TNFα) are usually observed in majority of the patients during febrile attacks.
New treatment modalities have been developed based on recent advances in pathogenesis of MKD/HIDS. Stemming from the proposed mechanism of inflammasome activation, IL-1 pathway appears to be the most effective therapeutic target to date.
Early diagnosis and treatment are crucial in MKD/HIDS as it can prevent irreversible organ damage and improve quality of life of patients, whose daily activities, education, and employment are often affected by frequent febrile attacks.
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