Disorders of red cell membrane

Abstract

Summary Studies during the last three decades have enabled the development of detailed molecular insights into the structural basis of altered function in various inherited red cell membrane disorders. This review highlights our current understanding of molecular and mechanistic insights into various inherited red cell membrane disorders involving either altered membrane structural organization (hereditary spherocytosis, hereditary elliptocytosis and hereditary ovalocytosis) or altered membrane transport function (hereditary stomatocytosis). The molecular basis for the vast majority of cases of hereditary spherocytosis, elliptocytosis and ovalocytosis have been fully defined while little progress has been made in defining the molecular basis for hereditary stomatocytosis. Mutations in a number of distinct genes account for hereditary spherocytosis and elliptocytosis, while a single genetic defect accounts for all cases of hereditary ovalocytosis. Based on these molecular insights, a comprehensive understanding of the structural basis for altered membrane function has been developed. Loss of vertical linkage between membrane skeleton and lipid bilayer leads to membrane loss in hereditary spherocytosis, while weakening of lateral linkages between skeletal proteins leads to membrane fragmentation and surface area loss in hereditary elliptocytosis. Importantly, the severity of anaemia in both these disorders is directly related to extent of membrane surface area loss. Splenectomy results in amelioration of anaemia.

Characterization of iron metabolism and erythropoiesis in erythrocyte membrane defects and thalassemia traits

“…The result is large numbers of abnormally shaped erythrocytes, i.e. spherical (for hereditary spherocytosis -HS) or elliptical (for hereditary elliptocytosis -HE) rather than the normal biconcave disk shape 3 . These abnormal erythrocytes have a shorter than average life-span for normal red blood cells and die prematurely.…”

Additional erythrocytic and reticulocytic parameters helpful for diagnosis of hereditary spherocytosis: results of a multicentre study

“…This diagnostic tool is therefore much more efficient than single parameters (Ret/IRF index) or the existing rules (reticulocytosis, % microcytes [5,2,6], combination of increased MCHC with RDW [2,7] , combination of increased RDW with hyperdense cells (Hyperchromic cells) [2,8], combination of increased MCHC with increased hyperdense cells [2]). …”

“…Some authors recommend automated red cell indices to predict or identify HS. Increased parameters such as reticulocytosis, % microcytes [5,2,6], combination of increased Mean Corpuscular Haemoglobin Concentration (MCHC) with increased red distribution width (RDW) [2,7] , combination of increased RDW with hyperdense cells (Hyperchromic cells) [2,8], combination of increased MCHC with increased hyperdense cells [2], decreased red cell and reticulocyte surface area [9], discordance between the Cell Haemoglobin Concentration Mean (CHCM) and MCHC [8] or Mean Spherized Corpuscular Volume (MSCV) lower than Mean Cell Volume (MCV) [10] are used for HS screening. However, most of these parameters are mean parameters and none of the tests is efficient for HS screening, especially in mild forms (without anaemia, reticulocytes <6% and bilirubin 17.4-34.2µM) or carriers of an asymptomatic trait (without anaemia, slight reticulocytosis (1.5-3.0%) and slightly reduced haptoglobin) [3].…”

Hemolytic Crisis due to Parvovirus B19 in Hereditary Spherocytosis in Two Siblings

“…The main defect is erythrocyte membrane disorder, and cells display surface loss. Therefore, erythrocytes are spherocyte-shaped (1,2). In these patients, hemolytic, aplastic, and megaloblastic crises may occur due to viral infections suppressing the bone marrow.…”