title: Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.
abstract: Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.
authors.affiliation: Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Joachim B
authors.initials: JB
authors.lastname: Kunz
authors.affiliation: Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Saida
authors.initials: S
authors.lastname: Awad
authors.affiliation: Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Happich
authors.affiliation: Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Muckenthaler
authors.affiliation: Department of General Pediatrics, Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg, Heidelberg, Germany.|Laboratory for Metabolic Disorders, Children's Hospital, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.affiliation: Department of General Pediatrics, Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Gramer
authors.affiliation: Department of General Pediatrics, Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jürgen G
authors.initials: JG
authors.lastname: Okun
authors.affiliation: Department of General Pediatrics, Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
authors.affiliation: Department of Pediatric Oncology, Hematology, Oncology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany. andreas.kulozik@med.uni-heidelberg.de.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
mesh_terms: D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D059788:Dried Blood Spot Testing / Q000379:methods; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D015995:Prevalence; D012805:Sickle Cell Trait / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
keywords: Allele-specific PCR; Newborn screening; Prevalence; Sickle cell disease