The phenotype and genotype of mevalonate kinase deficiency: A series of 114 cases from the Eurofever Registry

OBJECTIVES: Mevalonate kinase deficiency (MKD) is a rare metabolic disease characterized by recurrent inflammatory episodes. This study aimed to describe the genotype, phenotype and the response to treatment in an international cohort of MKD patients. METHODS: All MKD cases were extracted from the Eurofever registry (EAHC Project No. 2007332), an international, multicenter registry that retrospectively collects data on children and adults suffering from autoinflammatory diseases. RESULTS: One hundred and fourteen MKD patients were included in this study. The median age of onset was 0.5 years. Patients had on average 12 episodes per year. Most patients had gastrointestinal symptoms (n=112), mucocutaneous involvement (n=99), lymphadenopathy (n=102) or musculoskeletal symptoms (n=89). Neurological complaints included headache (n=43), but also cerebellar syndrome (n=2) and mental retardation (n=4). AA-amyloidosis was noted in five patients, almost twice as many as expected from previous cohorts. Macrophage activation syndrome occurred in one patient. Between attacks patients were generally well, but 10-20% patients suffered from constitutional symptoms, such as fatigue, between febrile attacks. Patients with p.V377I/p.I268T compound heterozygosity suffered significantly more often from AA-amyloidosis. Patients without a p.V377I mutation suffered more often from severe musculoskeletal involvement. Treatment with NSAIDs could relieve symptoms. Steroids given during attacks, anakinra and etanercept appeared to improve symptoms and could induce complete remission in MKD patients. CONCLUSION: This study described the clinical and genetic characteristics of 114 MKD patients, which is the largest cohort studied so far. The clinical manifestations confirm earlier reports. However, the prevalence of AA-amyloidosis was far higher than expected. This article is protected by copyright. All rights reserved.