Hb Sun Prairie: diagnostic pitfalls in thalassemic hemoglobinopathies

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Hemoglobinopathies represent a diverse group of genetic blood disorders.
• Alpha-globin variants, such as Hb Sun Prairie, can present with varying clinical phenotypes.
• Understanding inheritance patterns is crucial for diagnosing and managing these conditions.

Observation:

• An Asian Indian family presented with two daughters affected by Hb Sun Prairie (alpha 2 130(H13)Ala-->Pro beta 2).
• Homozygous daughters exhibited chronic hemolysis, consistent with previous reports.
• Heterozygous parents were asymptomatic, displaying a thalassemia carrier phenotype, differing from prior observations.

Findings:

• The family demonstrated clear autosomal recessive inheritance for the Hb Sun Prairie variant.
• Globin chain biosynthesis ratios initially suggested beta-thalassemia, but sequence analysis excluded this.
• An inversion of the alpha/beta-globin chain biosynthesis ratio was observed, a potential diagnostic confounder.

Implications:

• This case highlights the complex and variable phenotypes associated with thalassemic hemoglobinopathies.
• Autosomal recessive inheritance is confirmed for this alpha-globin variant, unusual for helix H region variants.
• The inverted globin chain biosynthesis ratio underscores the challenges in diagnosing hemoglobinopathies and necessitates comprehensive genetic analysis.