Search

Objective: Mevalonic aciduria represents the most severe form of mevalonate kinase deficiency (MKD). Patients with mevalonic aciduria have an incomplete response even to high doses of anti-cytokine drugs such as anakinra or canakinumab and stem cell transplantation (SCT) represents a possible therapy for this severe disease., Methods: We report the first two children affected by severe MKD who received haploidentical α/β T-cell and B-cell depleted SCT. Both patients received a treosulfan-based conditioning regimen and one received a second haploidentical-SCT for secondary rejection of the first., Results: Both patients obtained a stable full donor engraftment with a complete regression of clinical and biochemical inflammatory signs, without acute organ toxicity or acute and chronic GvHD. In both, the urinary excretion of mevalonic acid remained high post-transplant in the absence of any inflammatory signs., Conclusion: Haploidentical α/β T-cell and B-cell depleted SCT represents a potential curative strategy in patients affected by MKD. The persistence of urinary excretion of mevalonic acid after SCT, probably related to the ubiquitous expression of MVK enzyme, suggests that these patients should be carefully monitored after SCT to exclude MKD clinical recurrence. Prophylaxis with anakinra in the acute phase after transplant could represent a safe and effective approach. Further biological studies are required to clarify the pathophysiology of inflammatory attacks in MKD in order to better define the therapeutic role of SCT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive inborn error of metabolism with an autoinflammatory phenotype that may be expressed as a spectrum of disease phenotypes, from those with prevailing autoinflammatory syndrome and variable response to anti-inflammatory therapies, to mevalonic aciduria, which is associated with dysmorphic features, severe neurologic involvement, and the worst prognosis. We describe a boy, aged 2 years, 10 months, with severe phenotype of mevalonate kinase deficiency who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical unrelated cord blood because his condition had failed to improve with antiinflammatory treatment as first-line therapy and an anticytokine drug as second-line therapy. The child had a sustained remission of febrile attacks and inflammation after transplant, and during a 5-year follow-up period, psychomotor and neurologic development were normal, without signs of underlying disease or late transplant-related effects. This case confirms that allogeneic HSCT is a safe and effective cure for patients affected by MKD in whom anticytokine drugs alone are insufficient for the management of autoinflammatory syndrome and for the unfavorable outcome of the disease., (Copyright © 2015 by the American Academy of Pediatrics.)

A correction to the article "Haploidentical α/β T-cell and B-cell depleted stem cell transplantation in severe mevalonate kinase deficiency" in an issue is presented.