Dyslipidemia in adults and genetic polymorphism in the mevalonate kinase gene, a systematic review

The presence of mutations in dyslipidemia-related genes is of great importance for the outcome of procedures on patients with elevated levels of HDL cholesterol. This systematic review aims to describe the genetic variants in the mevalonate kinase genes in adults with dyslipidemia. A systematic search of the following databases was conducted: Scopus, Web of Science, Google Scholar and Bireme, using the keywords: "Mevalonate Kinase Gene", "Dyslipidemia", "Genetic Polymorphism", linked using the term "AND". The inclusion criteria consisted of articles published between 2008 and 2018, written in Portuguese or English, while the exclusion criteria were the removal of duplicated articles, books, theses and bibliographic reviews, tests not conducted on humans, tests conducted on children and other genes evaluated. The articles listed in this review demonstrate the role of the genetic polymorphism of the mevalonate-kinase gene (MVK) in an adult population. A comparison of results from different studies is often complicated because of the diverse study variables such as: tests used, population studied. The studies described in this review demonstrated that there is an association between genetic profiles and dyslipidemia. Many studies have shown that, besides the external factors and individuals’ behavioral habits, the presence of mutations in the mevalonate kinase gene is associated with dyslipidemia.

A Case of Hyperimmunoglobulinemia D Syndrome Successfully Treated with Canakinumab

Hyperimmunoglobulinemia D syndrome is a rare autosomal recessive autoinflammatory disorder caused by mutations in the mevalonate kinase gene (MVK). In a proportion of patients, however, noMVKmutations are detected. Although various standard anti-inflammatory drugs have been tried, until now there is no consensus about how HIDS should be treated. We present a case of HIDS in an 8-year-old girl whose clinical picture had started before the end of the first year of life. The patient had consistently elevated IgD levels but no mutations were found after a full-length analysis of theMVKgene. The method ofMVKmutational analysis is presented in details. Treatment with canakinumab in a final single dose of 4 mg/kg every 4 weeks resulted in the disappearance of febrile attacks and a considerable improvement of patients’ quality of life during a 12-month follow-up period. The drug has been well tolerated, and no side effects were observed.

A Clinical Criterion to Exclude the Hyperimmunoglobulin D Syndrome (Mild Mevalonate Kinase Deficiency) in Patients with Recurrent Fever

Objective.The hyperimmunoglobulin D syndrome (HIDS) is an autosomal recessive autoinflammatory disease caused by mutations in the mevalonate kinase gene. Our objective was to define a clinical criterion able to exclude HIDS without the need of genetic testing.Methods.A recursive partitioning algorithm was applied to derive the clinical criterion in 149 patients with genetic testing in a French laboratory, among whom 35 had HIDS. The criterion was validated in 93 patients with genetic testing in a Dutch laboratory, among whom 28 had HIDS.Results.The most discriminatory composite clinical criterion satisfied by all patients with HIDS in the derivation group was [onset age < 5 years old OR (joint pain during attacks AND length of attacks < 14 days)]. It had a sensitivity of 100% (95% confidence interval 88% to 100%) and a specificity of 28% (95% CI 17% to 40%) in the validation group. If genetic testing had been limited to patients fulfilling this criterion, 18 tests (19%) would have been avoided in this highly selected validation sample, without missing a single patient with HIDS.Conclusion.Even among patients already selected by expert physicians, this criterion could help prevent unnecessary genetic testing, which is resource- and time-consuming.