Knowledge about globin genetics for precision diagnosis of hemoglobinopathies: A case Study

Area of Science:

• Hematology
• Medical Genetics
• Biochemistry

Background:

• Over 1,800 hemoglobin (Hb) variants exist, often detectable by chromatography and electrophoresis.
• Complex hemoglobinopathies may necessitate molecular analysis and gene sequencing for definitive diagnosis.

Observation:

• A newborn presented with an FC hemoglobin profile, suggesting Hb C/Beta0 thalassemia and heterozygous Hb B2 co-inheritance.
• Maternal Hb A2 absence and paternal high Hb A2 levels raised diagnostic suspicions.
• Initial chromatographic and electrophoretic analyses confirmed the profile but required further molecular investigation.

Findings:

• Molecular analysis confirmed Hb C heterozygosity in the proband and mother.
• Beta0-thalassemia (CD39) allele was identified in the father and proband.
• Homozygous Hb B2 (A2') was found in the mother, and heterozygous in the proband.
• Gene sequencing of HBB and HBD genes confirmed the complex hemoglobinopathy diagnosis.

Implications:

• Accurate diagnosis of hemoglobinopathies relies on understanding globin chain genetics.
• Refined laboratory methodologies are crucial for validating initial findings in complex cases.
• This case underscores the necessity of integrating molecular techniques with traditional methods for comprehensive hemoglobinopathy diagnosis.