title: Hereditary Xerocytosis due to Mutations inPIEZO1Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families.
abstract: 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.PIEZO1gene 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.
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Elisa
authors.identifier: 0000-0003-2812-8711
authors.initials: E
authors.lastname: Fermo
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vercellati
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Marcello
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Zaninoni
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: van Wijk
authors.affiliation: U.O.C. Pronto Soccorso, Pediatria Ambulatoriale e DH/MAC, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mirra
authors.affiliation: U.O.S.D. Genetica Medica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Curcio
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy; Universita degli Studi di Milano, Milano, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanella
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
authors.affiliation: U.O.C. Oncoematologia, U.O.S. Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bianchi