Mevalonate kinase deficiency syndrome with structural damage responsive to anakinra

Abstract

Sir, mevalonate kinase deficiency (MKD) syndrome is an autosomal recessive autoinflammatory disorder caused by mutations in the MVK gene. We describe the first case of MKD syndrome with structural damage successfully treated with anakinra. A 32-year-old French Caucasian woman experienced relapsing flares of progressively destructive bilateral and symmetrical polyarthritis involving small and large joints with morning stiffness (lasting 2–4 h). Synovial fluid, drained several times, was inflammatory and contained an average of 30 000 leucocytes/mm3 (98% neutrophils), without crystals or bacteria. X-rays detected joint-space narrowing and erosions in several joints (Fig. 1). She had three or four polyarthritis attacks/year, each lasting 2–3 weeks, associated with fever (38–39°C), chills, fatigue, headaches, maculopapular rash, diarrhoea, vomiting with severe abdominal pain (macroscopically inflammatory peritonitis without bacteria), splenomegaly, bronchopneumopathy, elevated ESR (40–100 mm/1st h) and high CRP (50–200 mg/l). Since childhood, no autoantibodies (rheumatoid factor, antinuclear antibodies, anti-citrullinated antibodies) have ever been detected. The extra-articular symptoms started at 3 months (1974) with flares occurring at irregular intervals; atypical systemic juvenile idiopathic arthritis (aSJIA) was diagnosed, but was reconsidered in 2004 when laboratory investigations showed high serum immunoglobulin D (IgD) [166.4 mg/l (28.2<normal range<141 mg/l)], elevated mevalonaciduria [19.2 mmol/mol of creatinine (normal range<1.3 mmol/mol)] and low mevalonate kinase activity in lymphocytes [0.7 μkat/kg of protein (2.5<normal range<7.8 μkat/kg)]. Sequencing of the 10 MVK-gene exons detected a four-base deletion (c.475–478 delACTG) and an undescribed Q390P mutation, but no mutations were found in the genes encoding cold-induced autoinflammatory syndrome 1 (CIAS1) or tumour necrosis factor-receptor–1A (TNFR1A). MKD or hyper-IgD syndrome (HIDS) was diagnosed.