First Cases of Hb Agrinio Described in Patients from the Republic of Macedonia. (2nd November 2017)

• Record Type: Journal Article
• Authors: Dimishkovska, Marija; Kuzmanovska, Maja; Kocheva, Svetlana; Martinova, Kata; Karanfilski, Oliver; Stojanoski, Zlate; Plaseska-Karanfilska, Dijana
• Is Part Of: Hemoglobin. Volume 41:Number 4/5/6(2017)
• Page Start: 308
• Page End: 310
• Publication Date: 2017-11-02
• Subjects: α-Thalassemia (α-thal) -- Hb Agrinio -- homozygotes -- Romani population; Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.1080/03630269.2017.1397016
• Languages: English
• ISSNs: 0363-0269

Abstract

Abstract: Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: –α 3.7 (rightward), –(α) 20.5 and – – MED I deletions and Hb Icaria [α142, Term→Lys (α2), HBA2 : c.427T>A] and polyadenylation signal (polyA) [AAT A AA>AAT G AA (α2), HBA2 : c.*92A>G] point mutations. Here, we report two unrelated patients from the Romani population in the Republic of Macedonia, homozygotes for the α2-globin gene variant Hb Agrinio [α29(B10)Leu→Pro; HBA2 : c.89T>C]. To date, Hb Agrinio has been described only in individuals of Greek, Cypriot and Spanish origin. Both of our patients had early presentation of the disease (3.5 years and 2 months, respectively) with frequent blood transfusions from early infancy. They have a severe intermediate phenotype of thalassemia (Hb H disease) with hemoglobin (Hb) levels of 7.8 and 7.7 g/dL, respectively. Although the HBA2 : c.89T>C mutation results in an α + allele, the severe phenotype of the homozygotes is due to the production of hyperunstable α chains that undergo post translational precipitation. This leads to a greater degree of red cell damage and hemolytic anemia. The detection of Hb Agrinio in two unrelated families of Romani ethnic origin, may suggest it is a founder mutation in this population living in the Republic of Macedonia. Considering the severity of the clinical presentation of the homozygotes or compound heterozygotes for this rare Hb variant, a targeted molecular screening for Hb Agrinio mutation carriers should be considered in all patients of Romani ethnic origin with manifested microcytosis.