Diverse Hematologic and Molecular Characteristics of Hemoglobin O-Arab in the Moroccan Population: Experience of Mohammed VI National Laboratory of Medical Analysis.

Introduction

Hb O-Arab is a rare β-globin mutation (c.364G>A) predominantly found in Mediterranean and Middle Eastern populations, yet seldom reported in Morocco.

We report four Sanger-confirmed cases of Hb O-Arab, identified within two months, highlighting heterogeneity and likely underdiagnosis in the Moroccan population.

Patients and methods

EDTA samples referred to Mohammed VI Laboratory of Medical Analysis (Casablanca, Morocco) underwent CBC on automated analyzers and hemoglobin capillary zone electrophoresis (CZE; Capillarys, Sebia). Cases with a variant co-migrating in the HbA2 zone were confirmed by Sanger sequencing of the β-globin gene.

Results

Four patients were enrolled, comprising three males and one female, two children (2 and 4 years) and 2 adults (30 and 37 years old). CZE revealed an abnormal fraction co-migrating with HbA2 in all cases, rendering phenotypic identification inconclusive. Sanger sequencing confirmed the Hb O-Arab variant (c.364G>A) in all four patients: two were heterozygous (A/O-Arab), one was a compound heterozygote with Hb S (S/O-Arab), and one carried homozygous Hb O-Arab.

CBC findings varied across genotypes. The S/O-Arab case showed severe anemia (Hb 7.72 g/dL, MCV 95 fl, MCHC 34 %), the homozygous O-Arab patient had near-normal values with a decreased MCHC (25.7%), and the two A/O-Arab heterozygotes ranged from a normal profile to microcytic anemia in a 2-year-old child (MCV 63.4 fL, MCHC 35.4%).

Conclusion

Despite rarity of Hb O-Arab, with moroccan literature confined to familial series and individual case reports, four cases were identified within only two months, suggesting underdiagnosis rather than true scarcity. These cases illustrate a wide phenotypic and genotypic spectrum: heterozygous, homozygotes, and severe anemia when coinherited with Hb S. As CZE alone fails to resolve Hb O-Arab from HbC, an integrated screening and diagnosis approach combining molecular testing with phenotypic methods, could enable O-Arab carriers’ identification and early premarital genetic counseling to prevent at-risk combinations.