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Co-Inheritance of alpha-thalassemia and sickle cell disease in a cohort of Angolan pediatric patients

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Abstract

The aim of this study was to explore the association between alpha-thalassemia, fetal hemoglobin, hematological indices, and clinical adverse events in Angolan sickle cell disease pediatric patients. A total of 200 sickle cell disease (SCD) children were sampled in Luanda and Caxito. A venous blood sample was collected and used for hematological analyses, fetal hemoglobin quantification, and genotyping of 3.7 kb alpha-thalassemia deletion by GAP-PCR. The frequency of the 3.7 kb alpha-thalassemia deletion in homozygosity was 12.5% and in heterozygosity was 55.0%. An increase in alpha-thalassemia frequency was observed in children older than 5 years old (11.7% vs. 13.00%). Furthermore, 3.7 kb alpha-thalassemia deletion homozygotes had a significantly higher age of the first manifestation, lower number of blood transfusions by year, higher hemoglobin, lower mean corpuscular volume, mean corpuscular hemoglobin, and lower hemolytic rate observed by a lower number of reticulocytes count. There were no differences in fetal hemoglobin between the three genotypes. Moreover, the number of stroke events, osteomyelitis, splenomegaly, splenectomy, and hepatomegaly were lower when alpha-thalassemia was co-inherited. For the first time in Angolan population, the effect of alpha-thalassemia deletion in sickle cell disease was analyzed and results reinforce that this trait influences the hematological and clinical aspects and produces a milder phenotype.

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Acknowledgements

We would like to thank all the children and caregivers that accept to participate in the study. Moreover, we would like to thank the CISA's Laboratory Team for all the support namely Ilda Jeremias, Miguel Panzo, Lucas Catumbela, Graciete Salvador, Isabel Valentim, and Félix Zagi.

Funding

This work was supported by the Fundação Para a Ciência e Tecnologia I.P./Aga Khan Development Network Project Number 330842553.

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Authors and Affiliations

  1. Centro de Investigação em Saúde de Angola (CISA), Caxito, Angola

    Brígida Santos & Miguel Brito

  2. Hospital Pediátrico David Bernardino (HPDB), Luanda, Angola

    Brígida Santos

  3. Health and Technology Research Center (H&TRC), Instituto Politécnico de Lisboa/Escola Superior de Tecnologia da Saúde (IPL/ESTESL), Lisbon, Portugal

    Mariana Delgadinho, Joana Ferreira & Miguel Brito

  4. Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Lisbon, Portugal

    Isabel Germano, Armandina Miranda & Paula Faustino

  5. Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisbon, Portugal

    Ana Paula Arez

  6. Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina de Lisboa, Lisbon, Portugal

    Paula Faustino

Authors
  1. Brígida Santos
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  2. Mariana Delgadinho
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  3. Joana Ferreira
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  4. Isabel Germano
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  5. Armandina Miranda
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  6. Ana Paula Arez
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  7. Paula Faustino
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  8. Miguel Brito
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Contributions

MB, BS, APA, and PF participated in the design of the study; MB, BS, MD, JF, PF, AM, IG contributed to data collection and data analysis; MB, BS, MD, JF, PF, AM, IG, APA, contributed to interpretation of results; MB, BS contributed to manuscript writing; All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

Corresponding author

Correspondence to Miguel Brito.

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Conflict of interest

The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.

Ethics approval

This study was approved by the Ethical Committee of the Ministry of Health of Angola (CE. Nº 040/2018), the Ethical Committee of ESTeSL (CE-ESTeSL-Nº.43-2018).

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Informed consent was obtained and signed by the caregivers of children.

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Santos, B., Delgadinho, M., Ferreira, J. et al. Co-Inheritance of alpha-thalassemia and sickle cell disease in a cohort of Angolan pediatric patients. Mol Biol Rep 47, 5397–5402 (2020). https://doi.org/10.1007/s11033-020-05628-8

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  • DOI: https://doi.org/10.1007/s11033-020-05628-8

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