HBB – Sickle Cell-Hemoglobin E Disease Syndrome

Compound heterozygosity for hemoglobin S and E alleles in HBB manifests as sickle cell-hemoglobin E disease syndrome, characterized by hemolytic anemia (HP:0001878) and vaso-occlusive crises precipitated by physiological stressors. A 55-year-old female of South Asian descent presented with acute left upper quadrant pain after high-altitude exposure, was found to have hemolytic anemia and >50% splenic infarction with hemorrhagic conversion, and was diagnosed by hemoglobin electrophoresis ([PMID:33052282]). Across 44 reported compound heterozygous probands, this autosomal recessive condition consistently leads to hemolysis and infarction in the setting of stress ([PMID:33052282]). No multi-family segregation data are available.

Pathogenicity is attributed to HbS polymerization under low oxygen tension exacerbated by co-inherited HbE, although no disease-specific functional studies have been conducted. Management aligns with sickle cell trait protocols, emphasizing hydration and analgesia, reserving anticoagulation for confirmed thromboembolic events. Further studies are needed to refine genotype–phenotype correlations and therapeutic guidelines in diverse populations.

References

• Cureus • 2020 • Hemoglobin SE Disease Presenting as a High-Altitude Massive Splenic Infarction Complicated by Hemorrhagic Conversion and Splenectomy. PMID:33052282

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