Our results suggest that minor elevations in temperature can set off a chain of events with MK becoming progressively rate-limiting, leading to a temporary deficiency of isoprenoid end-products, which induces inflammation and fever.
Here, we report a novel pathogenic mutation in the MVK gene as the cause of fever in a 44-year-old male patient with a history of fever over a period of 27 years.
Our results suggest that minor elevations in temperature can set off a chain of events with MK becoming progressively rate-limiting, leading to a temporary deficiency of isoprenoid end-products, which induces inflammation and fever.
Inclusion criteria were a MVK mutation-positive patient ≤16 years of age with more than three self-limiting episodes of fever >38.5°C associated with increased inflammation markers.
The pathophysiology of these disorders is not yet understood, but eventually will give insight into the in vivo role of mevalonate kinase and isoprenoid biosynthesis with respect to the acute phase response and fever.
Her 19-year old brother presented since the age of 1 year with prolonged episodes of fever and was diagnosed with HIDS at the age of 7 years based on clinical features and homozygosity for p.V377I mutation in MVK.
Resolving the complete pathophysiology of this disorder is a major challenge, but eventually will give insight into the in vivo role of MK and isoprenoid biosynthesis in inflammation and fever.