Mevalonate kinase deficiency nomenclature

Abstract

In the letter of Celsi et al. [1], the authors suggest dropping the names of hyper-IgD syndrome (HIDS) and mevalonate kinase deficiency (MKD) for this hereditary syndrome. They base their conclusion upon the fact that there is no correlation between serum IgD concentration and disease severity, that not all HIDS patients show elevated IgD, and that they do not believe in a causative association with mevalonate kinase. Through the years, several new names for this disease have been used or suggested. It was first called HIDS because of the observation of elevated IgD serum concentrations in patients [2]. It has also been referred to as Dutch-type periodic fever syndrome [3], MKD, and even mevalonate-associated periodic syndrome (MAPS), in analogy with cryopyrin-associated periodic syndrome (CAPS) and TNF receptor-associated periodic syndrome (TRAPS) [4]. We agree that indeed the name HIDS may cause confusion for physicians not familiar with this disease. Although a strongly increased IgD concentration gives a good clue for diagnosis if present, it cannot be used as a diagnostic tool. The name ‘‘MKD’’ also has its drawbacks. Deficiencies in mevalonate kinase lead to a continuum of disease phenotypes, with HIDS at the mild end and the more severe mevalonic aciduria at the other end [5, 6]. Recently, the phenotype associated with deficiency in mevalonate kinase was broadened by discovery of cases of disseminated superficial porokeratosis (DSAP) [7], as well as isolated retinitis pigmentosa [8] associated with mevalonate kinase gene mutations. Sometimes, changing the name of a disease may seem a logical step from the pathophysiological point of view. Accordingly, it is now consensus among specialists to use MKD as the overall name, instead of HIDS, although still specifying the type of disease with the designations HIDS (for the phenotype of fever episodes) or mevalonic aciduria (for the more severely affected patients). However, changing a name causes confusion throughout literature, and as such information to clinicians, researchers, as well as for patients becomes complicated and confusing. This is already very much the case for the field of hereditary autoinflammatory syndromes, making it rather inscrutable for newcomers. This of course is not the purpose of nomenclature. Name changes should be implemented with care, and only when there are solid grounds to do so. We feel that the arguments of the authors of this letter [1] to stop using the name ‘‘MKD’’ are not solid. They mainly base this on in silico SNP data and the suggestion that other novel, previously overlooked genes and mechanisms may play a role in modifying the clinical phenotype. These are merely indications that the pathophysiology of MKD could be more complicated than previously described. This is at present not supported by clinical evidence, and we feel this is not enough reason to reconsider an established concept at this moment. It will actually cause more confusion than anticipated and does not improve understanding at all. These diseases are very rare and not M. Stoffels J. W. M. van der Meer A. Simon (&) Department of Medicine, 463 Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands e-mail: a.simon@aig.umcn.nl