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HB KIRKLARELI (ΑH58L): SECOND DESCRIPTION IN A BRAZILIAN PATIENT WITH DYSPNEA AND O2 SATURATION FALL
Author(s): ,
Maria de Fatima Sonati
Affiliations:
Clinical Pathology,State University of Campinas-UNICAMP,Campinas,Brazil
,
Gisele Pedroso
Affiliations:
Clinical Pathology,State University of Campinas-UNICAMP,Campinas,Brazil
,
Paula Nascimento
Affiliations:
Clinical Pathology,State University of Campinas-UNICAMP,Campinas,Brazil
,
Dulcineia Albuquerque
Affiliations:
Hematology and Hemotherapy Center ,State University of Campinas-UNICAMP,Campinas,Brazil
,
Marcela Grigoleto
Affiliations:
Clinical Pathology,State University of Campinas-UNICAMP,Campinas,Brazil
,
Magnun Santos
Affiliations:
Clinical Pathology,State University of Campinas-UNICAMP,Campinas,Brazil
,
Fernando Costa
Affiliations:
Hematology and Hemotherapy Center,State University of Campinas-UNICAMP,Campinas,Brazil
Susan Jorge
Affiliations:
Clinical Pathology,State University of Campinas-UNICAMP,Campinas,Brazil
(Abstract release date: 05/17/18) EHA Library. de Fátima Sonati M. 06/14/18; 216137; PB1974
Maria de Fátima Sonati
Maria de Fátima Sonati
Contributions
Abstract

Abstract: PB1974

Type: Publication Only

Background
Hemoglobin (Hb) Kirklareli [α158(E7)His®Leu;HBA1:c.176A®T] was first described by Bissé et al. in 2016 as a new α-globin variant associated with iron deficiency and increased CO binding. It was found in a Turkish female patient with mild anemia and in her father, who was not anemic but was a smoker with high levels of HbCO. Studies with recombinant human Hb Kirklareli showed that the αH58L subunits autoxidize and lose hemin more rapidly than native α subunits causing rapid denaturation of the oxygenated variant under physiological conditions. On the other hand, the mutant α subunits showed a much higher affinity for CO than O2, which prevents denaturation and explains the phenotypic differences between the patient and her father. 

Aims
We found the Hb Kirklareli mutation in the α2-globin gene (HBA2:c.176A®T) of a Brazilian patient admitted to the university hospital with severe dyspnea and O2 saturation fall and in his father, who presented with normocytic and normochromic moderate anemia. Our patient is an 11-year-old White male of Portuguese descent with history of respiratory problems since he was 6-y-o. Cardiac and pulmonary functions, inhalation and perfusion scintigraphy and CT scan of thorax were normal as well as the bone marrow and peripheral blood examination (patient’s red blood cell parameters: RBC=4.62, Hb=12.2, Hct=37.8, MCV=81.8, MCH=26.4, RDW=12.7; his father: RBC=2.87, Hb=8.4, Hct=25.6, MCV=89.2, MCH=29.3, RDW=14.5). 

Methods
Hb Kirklareli could not be distinguished from Hb A by electrophoresis at alkaline pH and cation exchange high-performance liquid chromatography (HPLC); at acidic pH it migrated in between Hbs S and C and in isoeletricfocusing in between Hbs A and F. The reversed phase HPLC revealed a slower extra peak (15% of the total, heme+globins) corresponding to the mutant α-chain.

Results
Direct sequencing of the α-genes revealed heterozygosis for the CAC®CTC substitution at codon 58 of the alpha2-globin gene in both, patient and his father

Conclusion

To our knowledge, this is the second family reported with Hb Kirklareli. In this case the variant is not associated with iron deficiency. Neither the patient nor his father is a smoker; the father is anemic but the patient has normal Hb values. However, the patient has a long history of respiratory problems without any other cause being detected, suggesting that other studies are needed to better understand the clinical behavior of this variant and the compensatory mechanisms elicited by it.

Financial Support: Fapesp, CNPq, CAPES and Faepex-Unicamp - Brazil.

Session topic: 29. Enzymopathies, membranopathies and other anemias

Keyword(s): Anemia, Diagnosis, Hemoglobinopathy

Abstract: PB1974

Type: Publication Only

Background
Hemoglobin (Hb) Kirklareli [α158(E7)His®Leu;HBA1:c.176A®T] was first described by Bissé et al. in 2016 as a new α-globin variant associated with iron deficiency and increased CO binding. It was found in a Turkish female patient with mild anemia and in her father, who was not anemic but was a smoker with high levels of HbCO. Studies with recombinant human Hb Kirklareli showed that the αH58L subunits autoxidize and lose hemin more rapidly than native α subunits causing rapid denaturation of the oxygenated variant under physiological conditions. On the other hand, the mutant α subunits showed a much higher affinity for CO than O2, which prevents denaturation and explains the phenotypic differences between the patient and her father. 

Aims
We found the Hb Kirklareli mutation in the α2-globin gene (HBA2:c.176A®T) of a Brazilian patient admitted to the university hospital with severe dyspnea and O2 saturation fall and in his father, who presented with normocytic and normochromic moderate anemia. Our patient is an 11-year-old White male of Portuguese descent with history of respiratory problems since he was 6-y-o. Cardiac and pulmonary functions, inhalation and perfusion scintigraphy and CT scan of thorax were normal as well as the bone marrow and peripheral blood examination (patient’s red blood cell parameters: RBC=4.62, Hb=12.2, Hct=37.8, MCV=81.8, MCH=26.4, RDW=12.7; his father: RBC=2.87, Hb=8.4, Hct=25.6, MCV=89.2, MCH=29.3, RDW=14.5). 

Methods
Hb Kirklareli could not be distinguished from Hb A by electrophoresis at alkaline pH and cation exchange high-performance liquid chromatography (HPLC); at acidic pH it migrated in between Hbs S and C and in isoeletricfocusing in between Hbs A and F. The reversed phase HPLC revealed a slower extra peak (15% of the total, heme+globins) corresponding to the mutant α-chain.

Results
Direct sequencing of the α-genes revealed heterozygosis for the CAC®CTC substitution at codon 58 of the alpha2-globin gene in both, patient and his father

Conclusion

To our knowledge, this is the second family reported with Hb Kirklareli. In this case the variant is not associated with iron deficiency. Neither the patient nor his father is a smoker; the father is anemic but the patient has normal Hb values. However, the patient has a long history of respiratory problems without any other cause being detected, suggesting that other studies are needed to better understand the clinical behavior of this variant and the compensatory mechanisms elicited by it.

Financial Support: Fapesp, CNPq, CAPES and Faepex-Unicamp - Brazil.

Session topic: 29. Enzymopathies, membranopathies and other anemias

Keyword(s): Anemia, Diagnosis, Hemoglobinopathy

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