IllnessThalassemia alpha + thalassemia beta

NGS +

Sanger

Thalassemia syndromes are based on impaired globin chain synthesis. Alpha-thalassemias are most often caused by deletions of one or more of the four alpha-globin genes. The severity of the clinical pictures of the different alpha-thalassemia subtypes correlates with the number of HBA genes affected. Two alpha-thalassemias cause severe health problems, most notably Hb-Bart's hydrops fetalis syndrome (- -/- -; Hb-Bart syndrome, alpha-thalassemia major) and less dramatically HbH disease (- -/- alpha). Clinically inapparent is the minima form, alpha-thalassemia minor is detected by laboratory chemistry. HbH disease causes marked abnormalities of the blood count already in the neonatal age. Adults suffer from hemolytic anemia. Hb-Bart syndrome presents with severe anemia, hepatosplenomegaly, cardiac and urogenital malformations. The inheritance is complex in four affected lozi, and the expressivity is variable. Provided HBA deletions and sequence mismatches are excluded, very rarely deletions of the MCS-R2 region are detected upstream of the HBA gene cluster. Thus, the clinical diagnosis or suspicion can virtually always be excluded by an inconspicuous finding.

The classification of beta-thalassemias is based on clinical aspects into beta-thalassemia minor (heterozygous), beta-thalassemia major (homozygous, mixed heterozygous) and beta-thalassemia intermedia (usually with additional mitigating genetic factors). Beta-thalassemias are always caused by mutations of the HBB gene, which can practically always be detected. Alterations of the amino acid sequence in the beta-globin protein also practically always cause different separation behavior in hemoglobin electrophoresis. In pregnant women with iron deficiency anemia and simultaneous suspicion of thalassemia, HBB gene sequence analysis should be performed.

References: https://www.ncbi.nlm.nih.gov/books/NBK1435/

https://register.awmf.org/assets/guidelines/025-017l_S1_Thalassaemien_2023-02_1.pdf

-α3.7/-α3.7 Thalassemia

α-Thalassemias represent the most common genetic hemoglobin abnormalities, especially in (sub-)tropical regions. They are caused by decreased or absent production of α-globin chains. α-Thalassemias are quite heterogeneous at the clinical and molecular levels. Four clinical states with increased severity are distinguished: the asymptomatic state of the heterozygous mutation carrier, the α-thalassemia minor form, the intermediate form of hemoglobin H disease and the lethal Hb-Bart hydrops fetalis syndrome. α-Thalassemias are often caused by deletions affecting one or both α-globin genes. The most common deletions affect a single α-globin gene and result in mild α-thalassemia phenotypes (- α/α α). Reciprocal recombination between highly homologous regions, for example, results in a chromosome with a 3.7-kb deletion containing only one α-gene (-α3.7). Two -α3.7 gene deletions in trans (-α3.7/-α3.7) are largely compensated by increased α-globin production of the remaining HBA1 alleles. Therefore, the corresponding symptomatology remains mostly quite mild - if clinical signs should arise at all. In general, thalassemia is inherited in an autosomal recessive manner; however, the inheritance can be quite complex as multiple genes can influence the production of hemoglobin. The -α3.7 deletion is one of the most common α-α-thalassemia alterations and is detected in virtually all cases by Hb electrophoresis and appropriate molecular genetic methods.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1435/

• Alias: Alpha Thalasämie
• Alias: Alpha-thalassemia intermedia
• Alias: Beta Thalassämie
• Alias: Beta-thalassemia
• Allelic: Delta-beta thalassemia (HBB)
• Allelic: Erythrocytosis 6 (HBB)
• Allelic: Erythrocytosis 7 (HBA1, HBA2)
• Allelic: Heinz body anemia (HBA1, HBA2)
• Allelic: Heinz body anemia (HBB)
• Allelic: Hemoglobin H disease, deletional + nondeletional, HbH disease (HBA1, HBA2)
• Allelic: Hereditary persistence of fetal hemoglobin (HBB)
• Allelic: Malaria, resistance to (HBB)
• Allelic: Methemoglobinemia, alpha type (HBA1)
• Allelic: Methemoglobinemia, beta type (HBB)
• Allelic: Sickle cell anemia (HBB)
• Allelic: Thalassemia, alpha (HBA1, HBA2)
• Allelic: Thalassemia-beta, AD inclusion-body (HBB)
• Thalassemia, alpha- (HBA1)
• Thalassemia, alpha- (HBA2)
• Thalassemia, beta (HBB)