Hemoglobin variant in disguise

Area of Science:

• Hematology
• Clinical Genetics
• Biochemistry

Background:

• Hemoglobinopathies encompass a spectrum of genetic disorders affecting hemoglobin (Hb) synthesis or structure.
• Over 1000 identified Hb variants range from clinically silent to severe, necessitating accurate diagnostic methods.
• Phenotypic analysis using electrophoresis and chromatography is common, but molecular genetic testing offers definitive identification.

Observation:

• A 23-month-old male presented with electrophoretic results suggestive of HbS trait, including HbA (39.4%) and HbS (48.5%).
• Unusual findings included a higher-than-expected HbS percentage and slightly elevated HbF and HbA2 levels without typical thalassemic indices.
• The patient remained clinically asymptomatic, thriving without any hemoglobinopathy-related complications.

Findings:

• Molecular genetic analysis revealed compound heterozygosity for HbS and the extremely rare beta-chain variant, Hb Olupona.
• Hb Olupona mimics HbA on standard phenotypic analyses (capillary electrophoresis, acid/alkaline gel electrophoresis, HPLC), leading to misidentification.
• The fractional concentration of HbS was higher than typically observed in HbS trait due to the presence of Hb Olupona.

Implications:

• Unusual fractional concentrations of Hb variants warrant advanced diagnostic approaches like mass spectrometry or molecular genetic testing.
• Accurate identification of rare Hb variants is crucial for understanding disease mechanisms and genetic counseling.
• While Hb Olupona appears clinically insignificant, definitive molecular diagnosis prevents misclassification and ensures appropriate patient management.