Red cell ektacytometry in two patients with chronic hemolytic anemia and three new alpha-spectrin variants
Por:
Vives-Corrons, JL, Krishnevskaya, E, Hernandez-Rodriguez, I, Payan-Pernia, S, Sevilla, AFR, Badell, I
Publicada:
1 mar 2022
Ahead of Print:
1 nov 2021
Resumen:
Red blood cell (RBC) morphology is, in general, the key diagnostic feature for hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). However, in hereditary pyropoikilocytosis (HPP), the severe clinical form of HE, the morphological diagnosis is difficult due to the presence of a RBC morphological picture characterized by a mixture of elliptocytes, spherocytes, tear-drop cells, and fragmented cells. This difficulty increases in new-borns and/or patients requiring frequent transfusions, making impossible the prediction of the disease course or its severity. Recently, it has been demonstrated that the measurement of osmotic gradient ektacytometry (OGE), using a laser-assisted optical rotational ektacytometer LoRRca (MaxSis, RR Mechatronics), allows a clear differentiation between HS and HE, where the truncated osmoscan curve reflects the inability of the already elliptical cells to deform further under shear stress in the face of hypotonicity. In HPP, however, the RBCs appear to have a significantly decreased ability to maintain deformability in these conditions, and the classical trapezoidal profile of HE is less evident or indistinguishable from HS. Here, two unrelated patients with hereditary hemolytic anemia (HHA) due to HPP and HS, respectively, are described with the joint inheritance of a complex set of five genetic defects. Two of these defects are novel alpha-spectrin gene (SPTA1) variants, one is a microdeletion that removes the entire SPTA1 gene, and two are well-known low-expression polymorphic alleles: alpha-LELY and alpha-LEPRA. In the HPP patient (ID1), with many circulating spherocytes, the interactions between the two SPTA1 gene variants may lead, in addition to an elongation defect (elliptocytes), to a loss of membrane stability and vesiculation (spherocytes), and RBCs appear to have a significantly decreased ability to maintain deformability in hypotonic conditions. Due to this, the classical trapezoidal profile of HE may become less evident or indistinguishable from HS. The second patient (ID2) was a classical severe form of HS with the presence of more than 20% of spherocytes and few pincered cells. The severity of clinical manifestation is due to the coinheritance of a microdeletion of chromosome 1 that removes the entire SPTA1 gene with a LEPRA SPTA1 variant in trans. The diagnostic interest of both observations is discussed.
Filiaciones:
Vives-Corrons, JL:
Inst Leukaemia Res Josep Carreras IJC, Red Cell Pathol & Haematopoiet Disorders Rare Ana, Cami De Les Escoles S-N Badalona, Barcelona 08916, Spain
Krishnevskaya, E:
Inst Leukaemia Res Josep Carreras IJC, Red Cell Pathol & Haematopoiet Disorders Rare Ana, Cami De Les Escoles S-N Badalona, Barcelona 08916, Spain
Hernandez-Rodriguez, I:
Hosp Univ Germans Trias I Pujol, Haematol Dept, Barcelona, Spain
Payan-Pernia, S:
Virgen Rocio Univ Hosp, Inst Biomed Seville IBiS CSIC, Hematol Dept, Red Blood Cell Disorders Unit, Seville, Spain
Sevilla, AFR:
Hosp Univ Santa Creu & St Pau, Hematol Dept, Barcelona, Spain
Badell, I:
Hosp Univ Santa Creu & St Pau, Hematol Dept, Barcelona, Spain
Hosp St Joan Deu, Hosp Santa Creu & St Pau, Natl Reference Ctr CSUR Accreditat Hereditary Red, Hosp Univ Santa Creu & St Pau,Dept Pediat, Barcelona, Spain
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