title: Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia.
abstract: Severe congenital neutropenia (SCN) is characterized by low blood neutrophil counts, early bacterial infections, and risk of leukaemia development. As yet, no population-based incidence estimates of SCN have been reported. Children less than 16 years of age with SCN were sought in Sweden during the 20-year period 1987-2006 by a questionnaire to all Swedish Departments of Paediatrics and by reviewing the Swedish Health and Welfare Statistical Databases. Thirty-two patients were diagnosed with congenital neutropenia during this period. All received treatment with recombinant granulocyte-colony stimulating factor (G-CSF). Twenty-one patients were diagnosed as SCN or probable SCN, corresponding to 1·0 per 100,000 live births. Nine (43%) had ELANE mutations, four (19%) HAX1 mutations and eight (38%) were children with disease of unknown genetic aetiology. Four out of 21 patients (19%) developed myelodysplastic syndrome/leukaemia and three (14%) died, all with leukaemia. The cumulative incidence of myelodysplastic syndrome/leukaemia was 31%. The observed incidence of SCN in this population-based study was higher than previously estimated, possibly because genetic testing now can identify SCN cases previously thought to be idiopathic or benign neutropenia. The risk of developing myelodysplastic syndrome/leukaemia is considerable. ELANE mutations are the most commonly identified genetic defects.
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. goran.carlsson@ki.se
authors.forename: Göran
authors.initials: G
authors.lastname: Carlsson
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.forename: Elisabet
authors.initials: E
authors.lastname: Berglöf
authors.forename: Kristina
authors.initials: K
authors.lastname: Lagerstedt-Robinson
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000080984:Congenital Bone Marrow Failure Syndromes; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000235:genetics; D009503:Neutropenia / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult