title: The alpha-globin genotype does not influence sickle cell disease severity in a retrospective cross-validation study of the pediatric severity score.
abstract: To validate the recently proposed pediatric severity score (PSS) for sickle cell disease (SCD), we retrospectively assembled clinical data from a cohort of 122 patients with SCD (105 S/S or S/β(0) -thal. and 17 S/C) followed up for at least 2 years. Besides age and α- and β-globin genotypes, four new parameters were also tested against the PSS: duration of data assembly, neonatal screening, use of transcranial Doppler ultrasound to prevent vasculopathies and β-globin gene cluster haplotype. Once again, the PSS clearly differentiated patients by their β-globin genotype (P=0.004) but not by their age during data assembly (P=0.159). But, surprisingly, alpha-gene deletions were not associated with a lower PSS (P=0.604), possibly reflecting the opposite effects of α-thalassemia on global SCD severity. As for the newly tested parameters, the PSS appeared not to be influenced by the duration of data assembly (P=0.071) and neonatal screening (P=0.678) but rather by the introduction of transcranial Doppler ultrasound (P=0.006). Moreover, the Senegal haplotype at the homozygous state may be associated with a lower PSS. Methodologically, our data globally confirm the usefulness of the PSS to identify major etiological factors of SCD gravity. Nevertheless, the score is surely underestimated for patients who have been switched to a chronic therapy before the main SCD complications. Biologically, our study questions about the exact influence of α-thalassemia on global SCD severity.
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge (Centre de Référence des Thalassémies), Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Edouard Herriot, Hospices Civils & Université Claude Bernard-Lyon 1, Lyon, France. philippe.joly@chu-lyon.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.forename: Corinne
authors.initials: C
authors.lastname: Pondarré
authors.forename: Claire
authors.initials: C
authors.lastname: Bardel
authors.forename: Alain
authors.initials: A
authors.lastname: Francina
authors.forename: Cyril
authors.initials: C
authors.lastname: Martin
mesh_terms: D000755:Anemia, Sickle Cell / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D055542:alpha-Globins