Clinical and molecular characterization of Hb Coimbra [HBB: c.300T>A p.(Asp100Glu)] in a three-generation Italian family: From diagnostic pitfalls to vascular risk.

BACKGROUND

High oxygen-affinity hemoglobin (HOAH) variants are rare causes of familial secondary erythrocytosis. Hb Coimbra [HBB: c.300T>A p.(Asp100Glu)] is a rare variant that can mimic β-thalassemia traits on HPLC, leading to diagnostic delays.

CASE PRESENTATION: We describe a three-generation Italian family affected by Hb Coimbra. The 5-year-old female proband presented with asymptomatic erythrocytosis (Hb 15.9 g/dL) and a spurious hemoglobin A2 (HbA2) peak of 39.6% on cation-exchange HPLC. Family screening revealed that her father was managed with erythroexchange (EEX), while her paternal grandfather suffered two ischemic strokes in the absence of traditional cardiovascular risk factors. Diagnosis was confirmed via DNA sequencing.

CONCLUSIONS

This case highlights the importance of recognizing pathognomonic HPLC artifacts to avoid misdiagnosis. It also underscores the need for long-term vascular risk stratification in pediatric carriers, particularly when a family history of thrombotic events is present.