D2.376 - Mevalonate kinase deficiency: An analysis of a Slovakian Cohort of MKD patients

Mevalonate kinase deficiency (MKD, previously hyper-IgD syndrome) belongs to a group of rare monogenic autoinflammatory diseases. The clinical manifestation of diseases associated with MVK deficiency is variable, although recurrent febrile attacks accompanied by abdominal pain, lymphadenopathy, rash, joint involvement with elevation of serum inflammatory biomarkers during flare-up period are relatively typical for MKD. The mainstay of treatment is with inhibitors of the interleukin-1 (canakinumab, anakinra).

We performed a retrospective analysis of clinical data from the Slovak national cohort of patients with mevalonate kinase deficiency (MKD), including overall 5 patients diagnosed between 2014 and 2025.

Our cohort consists of 4 female patients and 1 male patient with MKD. The average age at the time of the disease onset was 8 months (range: 4            months to 1 year). In all patients, pathogenic variants (2 homozygotes, 3 compound heterozygotes) in the MVK gene were proven by genetic analysis. In the clinical picture, febrile attacks occurred in all 5 patients, arthralgia (4/5), abdominal pain (3/5), myalgia (3/5), rash (3/5), fatigue (2/5), tonsilitis (2/5), lymphadenopathy – abdominal or cervical (3/5) and aphthae (1/5). Elevation of serum amyloid during a flare-up-free period was noted in 3 patients and 4 patients had elevated concentrations of IgD. Organ amyloidosis (renal) was present in 1 patient. Inhibitors of IL-1 were used as a treatment option in all 5 patients. In one patient, MKD coexisted with a chronic inflammatory disease – hidradenitis suppurativa, and the patient was effectively treated with a combination of biological molecules against IL-1 and TNF- α.

 In Slovakia, the estimated prevalence of the disease is approximately 1: 1 083 000, similar to the estimated prevalence of MKD in Eastern and Central European countries (1.3:1 000 000). The clinical manifestation of MKD in our cohort is similar to that in other works by European authors. We confirm the effectiveness of treatment with IL-1 inhibitors, as well as the possibility of treatment with a combination of multiple biological molecules.