title: Current advances in the understanding and treatment of mevalonate kinase deficiency.
abstract: Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired mevalonate kinase activity. Complete impairment results in the severe metabolic disease, mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum IgD levels and inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs, corticosteroids, and biological agents that target specific cytokine pathways. In recent years, some studies have reported promising results for new biological drugs; however, these cases have failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management.
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit&#x00E0; degli Studi di Milano, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit&#x00E0; degli Studi di Milano, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Ascolese
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit&#x00E0; degli Studi di Milano, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Senatore
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Universit&#x00E0; degli Studi di Milano, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bosis
authors.affiliation: Periodic Fever Research Center, Department of Internal Medicine, Universit&#x00E0; Cattolica Sacro Cuore, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Verrecchia
authors.affiliation: Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Siena, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cantarini
authors.affiliation: Institute of Pediatrics, Universita Cattolica Sacro Cuore, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Rigante
mesh_terms: D006801:Humans; D007072:Immunoglobulin D / Q000502:physiology; D054078:Mevalonate Kinase Deficiency / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000628:therapy*
chemical_list: D007072:Immunoglobulin D