Scholarlink

Background <p>The clinical severity of β-thalassemia is largely influenced by the imbalance between α- and β-globin chain production. Triplication of the α-globin gene increases excess α chains and can worsen the phenotype of β-thalassemia carriers, potentially leading to thalassemia intermedia or severe anemia.</p> Case Presentation <p>We report an 8-year-old child with severe microcytic hypochromic anemia requiring repeated blood transfusions. Hemoglobin electrophoresis revealed elevated HbA₂ (6.3%) and HbF (8.6%). Molecular testing—including GAP-PCR, ARMS-PCR, Sanger sequencing, and MLPA—identified homozygous α-globin gene triplication (ααα^anti3.7/ααα^anti3.7), a heterozygous β-thalassemia mutation at codons 36–37 (HBB: c.112delT), and a novel HBB intronic variant (c.92 + 40T &gt; A). Both parents carried triplicated α-globin alleles, though neither exhibited hematologic disease; no β-globin mutations were detected in the mother. MLPA confirmed increased probe ratios consistent with six α-globin gene copies, explaining the patient’s marked imbalance in globin chain synthesis and severe clinical presentation.</p> Conclusion <p>This case demonstrates that homozygous α-globin triplication can significantly exacerbate the phenotype of heterozygous β-thalassemia, even in the presence of silent or asymptomatic parental carriers. Comprehensive molecular analysis—including evaluation for α-globin triplication—should be considered in β-thalassemia carriers presenting with unexpectedly severe anemia to ensure accurate diagnosis and guide appropriate clinical management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Severe Pediatric Anemia Due to Alpha-Globin Triplication, Codon 36–37 Mutation, and a Novel HBB Variant

  • 期刊论文

  • 发表日期：

    2026年7月11日

查看全文
  • Elnaz Vaziee,
  • Ardeshir Bahmanimehr,
  • Atefeh Bahmei,
  • Aliraze Sabegh,
  • Ghazaleh Qaedi,
  • Somayeh Montazeri

摘要

Background

The clinical severity of β-thalassemia is largely influenced by the imbalance between α- and β-globin chain production. Triplication of the α-globin gene increases excess α chains and can worsen the phenotype of β-thalassemia carriers, potentially leading to thalassemia intermedia or severe anemia.

Case Presentation

We report an 8-year-old child with severe microcytic hypochromic anemia requiring repeated blood transfusions. Hemoglobin electrophoresis revealed elevated HbA₂ (6.3%) and HbF (8.6%). Molecular testing—including GAP-PCR, ARMS-PCR, Sanger sequencing, and MLPA—identified homozygous α-globin gene triplication (ααα^anti3.7/ααα^anti3.7), a heterozygous β-thalassemia mutation at codons 36–37 (HBB: c.112delT), and a novel HBB intronic variant (c.92 + 40T > A). Both parents carried triplicated α-globin alleles, though neither exhibited hematologic disease; no β-globin mutations were detected in the mother. MLPA confirmed increased probe ratios consistent with six α-globin gene copies, explaining the patient’s marked imbalance in globin chain synthesis and severe clinical presentation.

Conclusion

This case demonstrates that homozygous α-globin triplication can significantly exacerbate the phenotype of heterozygous β-thalassemia, even in the presence of silent or asymptomatic parental carriers. Comprehensive molecular analysis—including evaluation for α-globin triplication—should be considered in β-thalassemia carriers presenting with unexpectedly severe anemia to ensure accurate diagnosis and guide appropriate clinical management.