Mevalonate kinase somatic mosaicism and bigenic genotypes may explain heterogeneity in mevalonate kinase deficiency

Results Case 1 A pediatric case with splenomegaly, cervical lymphoadenopathy, failure to thrive and anemia, was found to have two pathogenic MVK variants, p.V250I and p. L315G*51, and the Q705K variant on the NLRP3 gene, considered a functional polymorphism. Typical symptoms and a high level of urinal mevalonic acid allowed closure on MKD diagnosis this case. Case 2 A pediatric case with recurrent and vaccination triggered attacks of high fever, sore throat, cervical lymphadenopathy and abdominal pain since infancy was a carrier of the MEFV p.V726A variant. The patient was diagnosed with PFAPA and treated with steroids. In the last, 10 days long attack the patient developed arthritis, a maculopapular rash and high blood pressure. MKD genetic testing revealed two pathogenic MVK variants, p.V377I and p.G202R, confirming the diagnosis of MKD. Case 3 A patient with adult onset Still’s disease symptoms including fever attacks, arthralgia, urticaria, pericarditis, and partial response to NSAIDs was shown to have a rare MVK variant, p.R121W, and the NLRP3 p.Q705K functional polymorphism. The diagnosis is yet unresolved. Case 4 An adult patient developed high fever and abdominal pain lasting 2-3 and HLA-B51 positive aphthous stomatitis. We identified somatic mosaicism (22%) for a novel, p.Ala161Thr MVK variant. The patient’s attacks resolved with anti TNF treatment and the current diagnosis is Behcet’s disease.