Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report

Abstract

Background Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. Case presentation A 2-year-old male presented with an acute 7-day history of high-grade fever, abdominal pain, diarrhoea, rectal bleeding and extensive purpuric and necrotic lesions, predominantly affecting the lower limbs. He had been suffering from recurrent episodes of fever from early in infancy, associated with maculopapular/petechial rashes triggered by intercurrent infection, and after vaccines. Extensive infection screen was negative. Skin biopsy revealed small vessel vasculitis. Visceral digital subtraction arteriography was normal. With a diagnosis of severe idiopathic cutaneous vasculitis, he was treated with corticosteroids and mycophenolate mofetil. Despite that his acute phase reactants remained elevated, fever persisted and the vasculitic lesions progressed. Next-generation sequencing revealed compound heterozygous mutation in MVK c.928G > A (p.V310M) and c.1129G > A (p.V377I) while reduced mevalonate enzyme activity was confirmed suggesting a diagnosis of MKD as a cause of the severe vasculitis. Prompt targeted treatment with IL-1 blockade was initiated preventing escalation to more toxic vasculitis therapies and reducing unnecessary exposure to cytotoxic treatment. Conclusions Our report highlights the broad clinical phenotype of MKD that includes severe cutaneous vasculitis and emphasizes the need to consider early genetic screening for young children presenting with vasculitis to exclude a monogenic vasculitis which may be amenable to targeted treatment.

A case report of Hyper‐IgD syndrome in a 5‐year‐old girl with recurrent fever, skin rash, and arthralgia; novel MVK mutation (C.298G>A)

“…a 2‐year‐old boy who had suffered from frequent episodes of fever since early infancy with maculopapular/petechial rashes lasting 2–6 days every 2 weeks was reported. Moreover, WES demonstrated heterozygous mutation in MVK c.928G>A and c.1129G>A 18 . In the study by Aygun et al.…”

“…Moreover, WES demonstrated heterozygous mutation in MVK c.928G>A and c.1129G>A . 18 In the study by Aygun et al. a 16‐month‐old boy was presented with recurrent fever episodes, maculopapular rash and cervical lymphadenopathy.…”