- Oral presentation
- Open Access
- Published:
Diagnostic value of urinary mevalonic acid excretion in patietns with a clinical suspicion of mevalonate kinase deficiency (MKD)
Pediatric Rheumatology volume 13, Article number: O57 (2015)
Introduction
Mevalonate kinase deficiency (MKD) is a rare hereditary autoinflammatory syndrome, characterized by recurrent fever episodes with gastrointestinal complaints, rash and arthralgia. In patients suffering from MKD, the reduced enzyme activity leads to an accumulation of mevalonic acid which is excreted in the urine. Therefore, an elevated mevalonic acid excretion is suggestive of MKD. However, the diagnostic value of this analysis has not been investigated yet and remains unclear.
Objectives
To investigate the diagnostic value of urinary mevalonic acid excretion in patients with suspected MKD.
Patients and methods
In this retrospective analysis, all patients in whom both measurement of mevalonic acid and genetic testing had been performed in the preceding 17 years have been included. Samples were analyzed by using gas chromatography-mass spectrometry (GC-MS) and concentrations were expressed as mmol/mol creatinine. The excretion of mevalonic acid was compared with age dependent reference values, validated at our hospital. The presence of two pathogenic MVK mutations was considered to be the gold standard for the diagnosis of MKD.
Results
This study included 62 patients (33 male, 29 female, aged: 0-36 year) with clinical features suggestive of MKD.
Thirteen patients harboured two MVK mutations, twelve of them excreted elevated amounts of mevalonic acid. In one patient mevalonic acid could not be detected, despite the fact that urine was collected during a febrile episode. Six patients had an elevated mevalonic acid excretion, but harboured no MVK mutations. However, repeated measurements in all six patients were ultimately normal.
This resulted in a sensitivity of 92%, a specificity of 88%, a positive predictive value of 68% and a negative predictive value of 98%. The positive likelihood ratio is 7.7 and the negative likelihood ratio is 0.09.
Conclusion
MKD seems very unlikely in patients with a normal mevalonic acid excretion, but it cannot be excluded completely. Furthermore, a positive urinary mevalonic acid excretion requires MVK analysis to confirm the diagnosis MKD. However, as long as genetic testing is not widely available and affordable, measurement of urinary mevalonic acid is a fair way to select patients for MVK-gene analysis.
Author information
Authors and Affiliations
Rights and permissions
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
About this article
Cite this article
Jeyaratnam, J., ter Haar, N., de Sain-van der Velden, M. et al. Diagnostic value of urinary mevalonic acid excretion in patietns with a clinical suspicion of mevalonate kinase deficiency (MKD). Pediatr Rheumatol 13 (Suppl 1), O57 (2015). https://doi.org/10.1186/1546-0096-13-S1-O57
Published:
DOI: https://doi.org/10.1186/1546-0096-13-S1-O57
Keywords
- Genetic Testing
- Negative Likelihood Ratio
- Positive Likelihood Ratio
- Febrile Episode
- Gastrointestinal Complaint