First Cases of Hb Agrinio Described in Patients from the Republic of Macedonia.

Abstract

Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: -α3.7 (rightward), -(α)20.5 and - -MED I deletions and Hb Icaria [α142, Term→Lys (α2), HBA2: c.427T>A] and polyadenylation signal (polyA) [AATAAA>AATGAA (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.

• Authors: Marija Dimishkovska, Maja Kuzmanovska, Svetlana Kocheva, Kata Martinova, Oliver Karanfilski, Zlate Stojanoski, Dijana Plaseska-Karanfilska
• Journal: Hemoglobin (Hemoglobin) 2017 Jul - Nov Vol. 41 Issue 4-6 Pg. 308-310 ISSN: 1532-432X [Electronic] England
• PMID: 29219637 (Publication Type: Case Reports, Journal Article)

Chemical References

• Hemoglobins, Abnormal
• hemoglobin Agrinio

Topics

• Child
• Child, Preschool
• Female
• Hemoglobins, Abnormal (genetics, metabolism)
• Homozygote
• Humans
• Republic of North Macedonia
• alpha-Thalassemia (blood, genetics)