Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families
Hereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increa...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Case Reports in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2017/2769570 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562201788940288 |
|---|---|
| author | Elisa Fermo Cristina Vercellati Anna Paola Marcello Anna Zaninoni Richard van Wijk Nadia Mirra Cristina Curcio Agostino Cortelezzi Alberto Zanella Wilma Barcellini Paola Bianchi |
| author_facet | Elisa Fermo Cristina Vercellati Anna Paola Marcello Anna Zaninoni Richard van Wijk Nadia Mirra Cristina Curcio Agostino Cortelezzi Alberto Zanella Wilma Barcellini Paola Bianchi |
| author_sort | Elisa Fermo |
| collection | DOAJ |
| description | Hereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. We report the clinical, haematological, and molecular characteristics of four patients from two unrelated Italian families affected by HX, associated with beta-thalassemia trait and heterozygous pyruvate kinase deficiency, respectively. Two patients had been splenectomised and displayed thrombotic episodes. All patients had iron overload in the absence of transfusion, two of them requiring iron chelation. The diagnosis of HX was confirmed by LoRRca Osmoscan analysis showing a left-shifted curve. PIEZO1 gene sequencing revealed the presence of mutation p.E2496ELE, showing that this is one of the most frequent mutations in this disease. The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. The study underlines the importance of a precise diagnosis in HX, particularly in view of splenectomy, and the need of a molecular confirmation of suspected RBC enzymopathy. |
| format | Article |
| id | doaj-art-8b7f8c63ed534579880dfe03212bca26 |
| institution | Kabale University |
| issn | 2090-6560 2090-6579 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Hematology |
| spelling | doaj-art-8b7f8c63ed534579880dfe03212bca262025-02-03T01:23:16ZengWileyCase Reports in Hematology2090-65602090-65792017-01-01201710.1155/2017/27695702769570Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated FamiliesElisa Fermo0Cristina Vercellati1Anna Paola Marcello2Anna Zaninoni3Richard van Wijk4Nadia Mirra5Cristina Curcio6Agostino Cortelezzi7Alberto Zanella8Wilma Barcellini9Paola Bianchi10U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, NetherlandsU.O.C. Pronto Soccorso, Pediatria Ambulatoriale e DH/MAC, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.S.D. Genetica Medica, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyU.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ItalyHereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. We report the clinical, haematological, and molecular characteristics of four patients from two unrelated Italian families affected by HX, associated with beta-thalassemia trait and heterozygous pyruvate kinase deficiency, respectively. Two patients had been splenectomised and displayed thrombotic episodes. All patients had iron overload in the absence of transfusion, two of them requiring iron chelation. The diagnosis of HX was confirmed by LoRRca Osmoscan analysis showing a left-shifted curve. PIEZO1 gene sequencing revealed the presence of mutation p.E2496ELE, showing that this is one of the most frequent mutations in this disease. The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. The study underlines the importance of a precise diagnosis in HX, particularly in view of splenectomy, and the need of a molecular confirmation of suspected RBC enzymopathy.http://dx.doi.org/10.1155/2017/2769570 |
| spellingShingle | Elisa Fermo Cristina Vercellati Anna Paola Marcello Anna Zaninoni Richard van Wijk Nadia Mirra Cristina Curcio Agostino Cortelezzi Alberto Zanella Wilma Barcellini Paola Bianchi Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families Case Reports in Hematology |
| title | Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families |
| title_full | Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families |
| title_fullStr | Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families |
| title_full_unstemmed | Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families |
| title_short | Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families |
| title_sort | hereditary xerocytosis due to mutations in piezo1 gene associated with heterozygous pyruvate kinase deficiency and beta thalassemia trait in two unrelated families |
| url | http://dx.doi.org/10.1155/2017/2769570 |
| work_keys_str_mv | AT elisafermo hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT cristinavercellati hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT annapaolamarcello hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT annazaninoni hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT richardvanwijk hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT nadiamirra hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT cristinacurcio hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT agostinocortelezzi hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT albertozanella hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT wilmabarcellini hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies AT paolabianchi hereditaryxerocytosisduetomutationsinpiezo1geneassociatedwithheterozygouspyruvatekinasedeficiencyandbetathalassemiatraitintwounrelatedfamilies |