title: A novel missense mutation in MVK associated with MK deficiency and dyserythropoietic anemia.
abstract: Mevalonate kinase deficiency (MKD) is a rare inborn error of metabolism caused by mutations in the mevalonate kinase (MVK) gene. The clinical phenotype is variable, ranging from the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to mevalonic aciduria (MA), a severe metabolic disease. We report here for the first time (to our knowledge) the case of a patient with MKD and congenital dyserythropoietic anemia. Clinical and laboratory characteristics of inflammatory attacks were compatible with HIDS, but mild dysmorphic features and elevated urinary mevalonic acid levels in the absence of an inflammatory attack suggested an intermediate phenotype between HIDS and MA. Genomic sequencing of the MVK gene revealed compound heterozygosity for a missense mutation previously described in MA (V310M) and a novel missense mutation (Y116H). By contrast, sequencing of the novel CDAII (SEC23B) gene revealed no mutations, suggesting that the bone marrow abnormalities were causally related to the MKD. Treatment with corticosteroids and colchicine directed at controlling the autoinflammatory disease resulted in improvement of the anemia.
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
authors.forename: Ayman
authors.initials: A
authors.lastname: Samkari
authors.forename: Arturo
authors.initials: A
authors.lastname: Borzutzky
authors.forename: Elisa
authors.initials: E
authors.lastname: Fermo
authors.forename: Diana O
authors.initials: DO
authors.lastname: Treaba
authors.forename: Fatma
authors.initials: F
authors.lastname: Dedeoglu
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Altura
mesh_terms: D000742:Anemia, Dyserythropoietic, Congenital / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D054078:Mevalonate Kinase Deficiency / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics*
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase