β‐Thalassemia pathogenic variants in a cohort of children from the East African coast

Abstract

Backgroundβ‐Thalassemia is rare in sub‐Saharan Africa. Previous studies have suggested that it is limited to specific parts of West Africa. Based on hemoglobin A2 (HbA2) concentrations measured by HPLC, we recently speculated that β‐thalassemia might also be present on the East African coast of Kenya. Here, we follow this up using molecular methods.MethodsWe used raised hemoglobin A2 (HbA2) values (> 4.0% of total Hb) to target all HbAA members of a cohort study in Kilifi, Kenya, for HBB sequencing for β‐thalassemia (n = 99) together with a sample of HbAA subjects with lower HbA2 levels. Because HbA2 values are artifactually raised in subjects carrying sickle hemoglobin (HbS) we sequenced all participants with an HPLC pattern showing HbS without HbA (n = 116) and a sample with a pattern showing both HbA and HbS.ResultsOverall, we identified 83 carriers of four separate β‐thalassemia pathogenic variants: three β0‐thalassemia [CD22 (GAA→TAA), initiation codon (ATG→ACG), and IVS1‐3ʹ end del 25bp] and one β+‐thalassemia pathogenic variants (IVS‐I‐110 (G→A)). We estimated the minimum allele frequency of all variants combined within the study population at 0.3%.Conclusionsβ‐Thalassemia is present in Kilifi, Kenya, an observation that has implications for the diagnosis and clinical care of children from the East Africa region.

Case Report: β-thalassemia major on the East African coast

“…The mutation responsible disrupts the transfer RNA binding site to result in a β 0 form of the disease. It appears to be rare in other populations: only 45 carriers have been reported in the literature to date, 20 of which were from our recently reported study ( Macharia et al ., 2020 ). Other reports of carriers have come from a wide range of countries including Switzerland ( Beris et al ., 1993 ), Belgium ( Wildmann et al ., 1993 ), Russia ( Molchanova et al ., 1998 ), India ( Gorakshakar et al ., 2018 ; Gupta et al ., 2002 ) and the former Yugoslavia ( Jankovic et al ., 1990 ).…”

“…We have previously estimated the birth prevalence of β-thalassemia major in our local community at approximately 1 in 100,000 ( Macharia et al ., 2020 ). Nevertheless, low awareness of this condition among clinicians and the low availability of diagnostic facilities within the region mean that historically, individuals with β-thalassemia major have probably been misdiagnosed with other conditions such as sickle cell anemia or iron deficiency anemia as was the case with this child.…”

Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa

“…Six children were found to be ineligible after DNA testing confirmed sickle cell trait. All of the other children were confirmed to have HbSS, and specifically none had heterozygous beta thalassemia trait that is present in East Africa [28]. Alpha thalassemia trait was common with half of the study participants having either 1 gene deletion (38%) or 2 gene deletions (12%).…”

Manifestações clínicas da beta talassemia maior na população pediátrica: Uma revisão sistemática

“…Neste âmbito, um estudo publicado por Macharia et al (2020) demonstrou que aproximadamente 0,6% da população de Kilifi, cidade da Quênia, na Costa Leste da África, é portadora de uma variante patogênica de talassemia que leva a BTM. Este dado foi considerado extremamente importante, pois, até então, não havia sido identificado anteriormente nenhum caso suspeito de BTM na prática clínica nesta localidade, uma vez que esta enfermidade é considerada extremamente rara na África Subsaariana.…”