Mutational Spectrum and Geographic Distribution of Alpha-thalassemia in an Adult Microcytic and/or Hypochromic Population Living in Portugal: Results from the First National Health Examination Survey (INSEF 2015)

Santos, Daniela; Kislaya, Irina; Lopes, Pedro; Matias-Dias, Carlos; Barreto, Marta; Faustino, Paula

http://hdl.handle.net/10400.18/7446

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Abstract(s)

Alpha-thalassemia (α-thal) is one of the most common monogenic disorders in the world. Its clinical severity varies from almost asymptomatic, mild microcytic hypochromic anemia, to a lethal hemolytic condition, depending on the number of affected α-globin genes (1 to 4). The disease is most commonly originated by deletions on 16p13.3. The aim of this study was to identify the molecular basis, geographic distribution and prevalence of mild forms of α-thal in Portugal. This is a cross-sectional population-based study, based on the first Portuguese National Health Examination Survey (INSEF), which included individuals living in Portugal for more than 12 months, aged between 25 and 74 years old. For this INSEF sub-study, we analysed 4812 participants from whom a Complete Blood Count was performed and selected the 204 participants presenting red blood cell microcytosis (Mean Corpuscular Volume, MCV <80fL) and/or hypochromia (Mean Corpuscular Hemoglobin, MCH <27pg). DNA from these samples was used to search for deletions in HBA cluster by Gap-PCR and Multiplex Ligation-dependent Probe Amplification. We found 52 individuals heterozygous for the -α3.7kb deletion, one homozygous for this deletion and one heterozygous for the -α4.2kb deletion. Two cases presented triplicated α-globin genes (αααanti 3.7kb). Thus, α-thal was observed in 54 individuals (26.5 %) of the analysed population. Carriers of the –α3.7kb deletion have hypochromic red blood cells (MCH mean 26.0 ± 0.9 pg) but normal or borderline volume (MCV mean 81.4 ± 2.7 fL). The geographic distribution of affected participants showed two regions with highest prevalence of α-thal: LVT and RA Madeira. Although the mild forms of α-thal themselves are of no clinical significance, their major importance is the modifying effect that they have on various severe forms of β-thalassemia and sickle cell disease. Furthermore, α-thal trait can be confused with iron deficiency anemia as the hematological parameters are quite similar. Therefore, iron status should be properly assessed to distinguish between the two conditions and α-thal confirmation at DNA level is necessary for a definitive diagnosis.

Keywords

Alpha-thalassemia Mutational Spectrum Geographic Distribution Portugal Gap-PCR MLPA National Health Examination Survey INSEF Hemoglobinopatias Alfa-talassémia Doenças Genéticas Estados de Saúde e de Doença Portugal