Methods: Only one specialized laboratory in the country provides urine MVA measurement and since 2012 also MVK gene analysis. All patients with positive MVA detected between Jan 2004 and Dec 2016 and/or those with 2 MVK gene mutations were retrieved and their electronic records reviewed by treating physicians.

Results: : Five patients from 2 other institutions were identified on top of the original 8 cases (11 females), all Caucasians. Only patients with MKD phenotype and/or confirmed MVK mutations had positive urine MVA. Median age at onset was 15 (1-36) months, diagnostic delay was 8.2 (1-25.5) years. (Table) Gastrointestinal and joint symptoms were present in 54 and 62% of cases, respectively, 7 patients (54%) had cervical lymphadenopathy and 5 (38%) splenomegaly. “Severe” symptoms that lead to the introduction of biologics in 7 patients included high episode frequency interfering with daily activities (n=6), splenomegaly (n=3) and renal amyloidosis with onset at 5 years of age (n=1, patient 6). Patient 12 died in early infancy with the picture of fulminant HLH. When her younger sister presented with similar symptoms at 3 weeks of age she rapidly received HSCT for suspected unknown primary HLH. Only after her recovery results of the WES became available and confirmed MKD, which was then found also in her sister’s stored DNA. Patient 5 had nearly complete resolution of symptoms without therapy during her uneventful pregnancy and gave birth to healthy twins. Her disease returned post-delivery in full severity and her treatment response remains unsatisfactory.

Conclusion:  : Over the past 12 years 13 Czech patients were diagnosed with MKD. The genotype spectrum was similar to that reported with the p.V377I mutation being the most prevalent. Unlike other series, high proportion of patients (n=9, 69%) had severe or life-threatening phenotype requiring biologic therapy or HSCT. We learned that macrophage activation triggered by MKD may mimic primary HLH in neonatal period and that amyloidosis may complicate untreated MKD very early. Similarities with the more common and benign PFAPA syndrome have lead us to screen all suspected PFAPA patients for urine MVA.