Modification of hemoglobin H disease by sickle trait

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Hemoglobin H (Hb H) disease, a form of alpha-thalassemia, is typically characterized by the presence of Hb H.
• The co-occurrence of Hb H disease and sickle trait is rare, possibly due to factors influencing Hb H formation.

Observation:

• A boy presented with microcytic, hypochromic anemia, splenomegaly, and rare erythrocyte inclusions.
• Electrophoresis revealed Hb S, persistent Hb Bart's, but no Hb H.
• Molecular analysis showed the patient possessed only one alpha-globin gene.

Findings:

• The patient had a low alpha/non-alpha globin chain synthesis ratio, indicating impaired alpha-globin production.
• Bone marrow morphology suggested early precipitation of an unstable hemoglobin.
• The absence of detectable Hb H was attributed to reduced beta(A) globin availability and altered globin chain affinities due to the co-inherited beta-S gene.

Implications:

• The presence of the sickle cell trait (beta-S gene) can modify the clinical expression of hemoglobin H disease.
• Understanding these genetic interactions is crucial for diagnosing and managing rare hemoglobinopathies.