Highlights
- •Classification criteria help diagnose mevalonate kinase deficiency.
- •Ischemic stroke is a potential complication of mevalonate kinase deficiency.
- •Anti-interleukin-1 therapy prevents recurrent autoinflammatory attacks.
Abstract
Objectives
Mevalonate kinase deficiency (MKD) is an autosomal recessive autoinflammatory disease
characterized by recurrent systemic inflammation attacks. Despite interconnections
with inflammation, thrombosis is rare or underreported in MKD. Our goal is to report
evidence of uncontrolled inflammation as the cause of ischemic stroke.
Materials and Methods
Case report.
Results
A 39-year-old French-Canadian patient consulted for stroke. He reported a previous
diagnosis of familial Mediterranean fever and hospitalizations nearly monthly since
birth for recurrent inflammatory attacks despite colchicine prophylaxis. Attacks were
triggered by infections or stress, lasted 3-7 days, and included fever up to 41°C,
painful lymphadenopathies, abdominal pain, polyarthralgia and maculopapular rash.
Stroke culminated his most recent inflammatory attack. Brain MRI confirmed an acute
infarct, without chronic ischemic damage. Blood tests documented increased C-reactive
protein, amyloid A and immunoglobulin-D. Prothrombotic and autoantibody tests, cervicocephalic
CT-angiography, echocardiography, cardiac monitoring, and toxic screen were unremarkable.
Infections were excluded. His only sister had similar attacks. In both cases, sequencing
of 32 autoinflammatory-associated genes identified two pathogenic mevalonate kinase mutations. Their non-consanguineous parents, half-brother and four children were
asymptomatic. Following treatment with anti-interleukin-1beta monoclonal antibodies,
he no longer had inflammatory attacks or stroke in >4 years.
Conclusion
This MKD patient experienced an ischemic stroke during an attack, attributed to uncontrolled
inflammation. Investigations excluded other stroke etiologies. Recurrent febrile attacks
starting before age 1 and lasting >3 days, gastrointestinal symptoms, painful lymphadenopathies,
maculopapular rash, triggers, aphthous stomatitis, non-Mediterranean ancestry, and
ineffectiveness of colchicine prophylaxis are consistent with MKD. Anti-interleukin-1
therapy prevents recurrent autoinflammatory attacks.
Keywords
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Article info
Publication history
Published online: October 12, 2022
Accepted:
September 10,
2022
Received in revised form:
September 3,
2022
Received:
February 13,
2022
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106780
Copyright
© 2022 Elsevier Inc. All rights reserved.
