Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory
metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high
fever, abdominal distress, diffuse
joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum
immunoglobulin D (
IgD) levels (
hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired
mevalonate kinase activity. Complete impairment results in the severe
metabolic disease,
mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum
IgD levels and
inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs,
corticosteroids, and
biological agents that target specific
cytokine pathways. In recent years, some studies have reported promising results for new
biological drugs; however, these cases have failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management.