HbS/β+ thalassemia: Really a mild disease? A National survey from the AIEOP Sickle Cell Disease Study Group with genotype-phenotype correlation

Eur J Haematol. 2020 Mar;104(3):214-222. doi: 10.1111/ejh.13362. Epub 2019 Dec 12.

Abstract

Objectives: HbS/β+ patients' presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/β+ patients, with genotype-phenotype correlation, in order to offer guidance for clinical management of such patients.

Methods: Retrospective cohort study of HbS/β+ patients among 15 AIEOP Centres.

Results: A total of 41 molecularly confirmed S/β+ patients were enrolled (1-55 years, median 10.9) and classified on β+ mutation: IVS-I-110, IVS-I-6, promoter, and "others." Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS-I-110 group presented the lowest median age at first SCD-related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS-I-6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers.

Conclusions: HbS/β+ is not always a mild disease. Patients with IVS-I-110 mutation could benefit from a standard of care like SS and S/β° patients. Standardization of treatment is needed.

Keywords: HbS/β+ thalassemia; Italy; Sickle cell disease; children; genotype; phenotype.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Anemia, Sickle Cell / diagnosis*
  • Anemia, Sickle Cell / epidemiology
  • Anemia, Sickle Cell / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genetic Association Studies
  • Genotype*
  • Hemoglobin, Sickle / genetics*
  • Humans
  • Infant
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Phenotype*
  • Public Health Surveillance
  • Retrospective Studies
  • Young Adult
  • beta-Globins / genetics*
  • beta-Thalassemia / diagnosis*
  • beta-Thalassemia / epidemiology
  • beta-Thalassemia / genetics*

Substances

  • Hemoglobin, Sickle
  • beta-Globins