Genotype–phenotype correlation among beta-thalassemia and beta-thalassemia/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis

Abstract

IntroductionBeta-thalassemia is a group of inherited hemolytic anemias and one of the most common genetic disorders in Thailand. The clinical spectrum of beta-thalassemia disease ranges from mild to severe clinical symptoms including mild beta-thalassemia intermedia (TI) and severe beta-thalassemia major (TM).ObjectiveThis study aimed to determine the correlation between beta-globin gene (HBB) mutations and their phenotypic manifestations by evaluating patients’ clinical characteristics, transfusion requirements, growth and hematologic parameters, and hemoglobin typing among pediatric patients treated at Phramongkutklao Hospital.Materials and methodsSeventy beta-thalassemia patients, including 63 with beta-thalassemia/hemoglobin E (HbE) and 7 with either homozygous or compound heterozygous beta-thalassemia, were enrolled in this study. Their clinical presentation, growth parameters and laboratory findings were reviewed and analyzed. The mean follow-up time was 10.52±5.62 years. Mutation analysis in each individual was performed using multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene and gap PCR for 3.4 kb deletion detection.ResultsAll 7 homozygous and compound heterozygous beta-thalassemia patients were classified in TM. Among 63 patients with beta-thalassemia/HbE, 58 were classified in TM and 4 were classified in TI. Mean age at diagnosis was 0.8±0.49 years for homozygous or compound heterozygous beta-thalassemia and 3.43±3.5 years for beta-thalassemia/HbE. The most common HBB mutation was HBB:c.126_129delCTTT [codon 41/42 (-TCTT)] found in 34 alleles (48.6%). The height for age was also lower in homozygous beta-thalassemia patients (<3rd percentile) compared to compound heterozygous beta-thalassemia patients (25–50th percentile).ConclusionThis study revealed a genotype–phenotype correlation of the most prevalent beta-thalassemia in Thai children using diagnostic capacity in genotypic analysis of HBB mutation. Our findings can provide a better prediction of clinical manifestation and severity by early identification of the type of the HBB mutations.

Efficacy of Oral Acetaminophen and Intravenous Chlorpheniramine Maleate versus Placebo to Prevent Red Cell Transfusion Reactions in Children and Adolescent with Thalassemia: A Prospective, Randomized, Double-Blind Controlled Trial

“…The prevalence of thalassemia traits in Thai population was reported to be 20–30% for α -thalassemia, 3-9% for β - thalassemia, and 20-30% for Hb E [ 10 , 11 ]. The diverse thalassemia genotypes found in this population results in different phenotypic characteristics and variation in transfusion requirements comparing to other diseases [ 12 , 13 ]. Given the clinical severity of ineffective erythropoiesis in patients with thalassemia disease, red blood cell (RBC) transfusion is considered as the mainstay of treatment in order to prolonged overall survival in most of the patients [ 14 , 15 ]; however, a risk of developing reactions from RBC transfusion is commonly reported and quite challenging since the reactions are difficult to predict in each individual patient [ 16 , 17 ].…”

Pregnancy and Childbirth: An Unexpected Cakewalk for a Mother With Beta Thalassemia Major Homozygous for IVS (G-C) Mutation

“…The existence of HbF enhancer loci probably has changed the clinical picture in our case. Also various genetic interactions in the beta globin gene and outside the gene can affect the phenotypic presentation in beta thalassemia [8][9][10][11].…”

Correlation of Cytogenetic, Molecular and Clinical Findings in Thalassemia Patients at a Tertiary Care Hospital

“…The underlying genetic mutation is one of the determinants of clinical presentation of beta thalassemia. [10] β-Thalassemia major patients have severe anaemia, microcytic and hypochromic anaemia and hepatosplenomegaly. These thalassemia patients generally come to medical attention within the first two years of life.…”

“…[17] Presently, the molecular basis (Mutation) of β-thalassemia has been studied worldwide. [10] Maximum thalassemia mutations are contributed by small deletions, insertions or point mutations within the coding regions (CDS: coding sequence) and the exon-intron junctions. [10] The prevalence of β-thalassemia trait was 2.78 % and range from 1.48 to 3.64 % in different states.…”

“…[10] Maximum thalassemia mutations are contributed by small deletions, insertions or point mutations within the coding regions (CDS: coding sequence) and the exon-intron junctions. [10] The prevalence of β-thalassemia trait was 2.78 % and range from 1.48 to 3.64 % in different states. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %).…”