Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children.
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.
Department of Paediatric Rheumatology, Children's Hospital, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. elke.lainka@uni-due.de
E
E
Lainka
U
U
Neudorf
P
P
Lohse
C
C
Timmann
M
M
Bielak
S
S
Stojanov
K
K
Huss
R
R
von Kries
T
T
Niehues
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors
D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase