The Prevalence of Hereditary Hemoglobin Disorders and Its Implications for Newborn Screening in Germany

Introduction: Hemoglobin disorders are among those hereditary diseases with evidence that an early diagnose and treatment improve the clinical outcome of affected children. So far hemoglobin disorders are not included in the German newborn screening program despite increased immigration from countries with populations at risk.

Methods: To determine the birth prevalence in a major German area we tested 16910 anonymized newborns from Hamburg. High pressure liquid chromatography (HPLC) and subsequent molecular-genetic testing were used for the detection and confirmation of sickle cell variant (HbS), of hemoglobin C (HbC) and of beta- and alpha-thalassemia variants.

Results: We found sickle cell disease (SCD) to be the most prevalent with a frequency of disease-consistent genotypes of 1 in 3382 newborns. The prevalence for sickle cell trait (SCT) was 1 in 301 births. Statistical analysis indicates with 96% probability a prevalence for SCD of at least 1 in 8455 births and for SCT of at least 1 in 393 births. Duffy-blood group typing showed evidence that affected children were likely of Sub-Saharan ancestry. More than 90% of the newborns found with SCD or SCT were of sub-Saharian ancestry, suggesting that in Hamburg mainly children from members of the African community are at risk for the hemoglobinopathy SCD. Our data indicate a 95% probability that the prevalence of SCD in Hamburg is at least 1,18/10.000 births.

Alpha Thalassemia trait had a prevalence of 1: 994, indicating with 97% probability a minimal prevalence of 1: 2114 births. In this study we did not find any child with beta-thalassemia major or HbH- disease, which indicates a birth prevalence of less than 1 in 16910 births during the study period.

32 chromatograms indicated heterozygosity for other hemoglobin variants and 1 pattern indicated homozygosity for HbCC.

Conclusion: Our study sustains the notion that newborn screening in areas that see significant immigration is necessary to provide early intervention with the framework of a public health initiative. As long as a nationwide screening in Germany is not yet implicated all high-risk infants (those of African, Mediterranean, Middle Eastern, Indian, Caribbean, and South and Central American ancestry) should receive a neonatal screening for SCD. Any high-risk infant not screened at birth, or for whom neonatal screening results cannot be documented, should be screened for hemoglobinopathies prior to 2 months of age.