Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children

• Published in: Rheumatology international Vol. 32; no. 10; pp. 3253 - 3260
• Main Authors: Lainka, E., Neudorf, U., Lohse, P., Timmann, C., Bielak, M., Stojanov, S., Huss, K., von Kries, R., Niehues, T.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-10-2012; Springer Nature B.V
• Subjects: Adolescent; Age of Onset; Child; Child, Preschool; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Germany - epidemiology; Heterozygote; Humans; Incidence; Infant; Male; Medicine; Medicine & Public Health; Mevalonate Kinase Deficiency - diagnosis; Mevalonate Kinase Deficiency - enzymology; Mevalonate Kinase Deficiency - epidemiology; Mevalonate Kinase Deficiency - genetics; Mevalonate Kinase Deficiency - therapy; Mutation; Original Article; Phenotype; Phosphotransferases (Alcohol Group Acceptor) - genetics; Prognosis; Prospective Studies; Rheumatology; Surveys and Questionnaires; Time Factors; Germany; HIDS; MVK gene; ESPED; Autoinflammatory disease; HRF
• ISSN: 0172-8172; 1437-160X
• DOI: 10.1007/s00296-011-2180-8

Autoinflammatory diseases (AIDs) are characterized by recurrent, self-limiting systemic inflammation. Disorders include hereditary recurrent fever (HRF) syndromes such as hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). To determine the incidence of HIDS and report clinical and genetic characteristics together with the underlying
MVK
genotypes in German children, a prospective active surveillance was conducted in Germany during a period of 3 years. Monthly inquiries were sent to 370 children’s hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to two laboratories (Laboratory-ESPED, n2) performing genetic analyses. Inclusion criteria were a
MVK
mutation–positive patient ≤16 years of age with more than three self-limiting episodes of fever >38.5°C associated with increased inflammation markers. Clinical, epidemiological, and genetic data were assessed via questionnaires. Eight out of 16 patients were identified in Clinic-ESPED (n1) and 15 of 16 in Laboratory-ESPED (n2). Clinical and laboratory surveys overlapped in 7 of 16 cases. Incidence of HIDS was estimated to be 0.39 (95% CI: 0.22, 0.64) per 10
6
person-years. HIDS symptoms generally started in infancy with recurrent fever episodes lasting 3–12 (median, 4.5) days and recurring every 1–12 weeks. Fever was accompanied by abdominal pain, vomiting, diarrhea, cervical lymphadenopathy, and sometimes by headache, skin and joint symptoms. The patients carried 11 different
MVK
mutations mostly in compound heterozygosity (75%, 12 out of 16). The most frequent mutation was p.Val377Ile (81%, 13 out of 16). In Germany, the incidence of HIDS is very low with 0.39 per 10
6
person-years.