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At least 19 recordsLinked to original sources
PubMed1990

Alteration of the erythrocyte membrane skeletal ultrastructure in hereditary spherocytosis, hereditary elliptocytosis, and pyropoikilocytosis.

The membrane skeleton of normal erythrocytes is largely organized into a hexagonal lattice of junctional complexes (JC) crosslinked by spectrin tetramers, and occasional double tetramers and hexamers. To explore possible skeletal alterations in hereditary spherocytosis (HS), elliptocytosis (HE), and pyropoikilocytosis (HPP), we have studied the ultrastructure of the spread membrane skeletons from a subpopulation of HS patients with a partial spectrin deficiency ranging from 43% to 86% of normal levels, and in patients with HPP who, in addition to a mild spectrin deficiency, also carried a mutant spectrin that was dysfunctional, thus reducing the ability of spectrin dimers to assemble into tetramers. Membrane skeletons derived from Triton-treated erythrocyte ghosts were examined by negative staining electron microscopy. HS membrane skeletons contained structural elements, consisting of JC and spectrin filaments similar to the normal skeleton. However, less spectrin filaments interconnected the JC, and the decrease of spectrin filaments attached to JC appeared to correlate with the severity of spectrin deficiency. Only in severe HS associated with severe spectrin deficiency was the loss of spectrin sufficient enough to disrupt the overall skeletal architecture. In contrast, membrane skeletons prepared from red blood cells (RBCs) of subjects with HPP were strikingly different from HS RBCs with a comparable degree of spectrin deficiency. Although HPP RBCs were only mildly deficient in spectrin, their skeletal lattice was grossly disrupted, in contrast to only mild ultrastructural abnormalities of HS membrane skeletons with a nearly identical degree of spectrin deficiency. Skeletons from patients with common mild HE or asymptomatic carriers, carrying the mutant spectrin but having normal spectrin content, exhibited a moderate disruption of the skeletal lattice. We propose that the above differences in skeletal ultrastructure may underlie differences in the biomechanical properties and morphology of HS, HE, and HPP RBCs.

Cytoskeleton↗
PubMed1997

[Hemochromatosis associated with hereditary spherocytosis].

Hereditary spherocytosis is a chronic hemolytic anemia that very infrequently produces severe iron overload. Only 15 cases of hereditary spherocytosis associated with hemochromatosis have been described previously. It was initially thought that hemochromatosis was the result of the increase of iron stores secondary to chronic hemolysis. Afterwards, it became apparent that iron overload could appear in patients splenectomized. This fact suggested that spherocytosis and idiopathic hemochromatosis could be inherited independently. We describe the case of a 45-year-old man, with known hereditary spherocytosis, splenectomized at 5 years of age, who developed iron overload which affected his heart, liver and pancreas.

Cardiomyopathies↗
PubMed1989

[The modified "pink test" in the diagnosis of hereditary spherocytosis].

Hereditary spherocytosis is still difficult to diagnose in some situations due to the existence of subclinical expressions and the lack of an accurate test with high sensitivity and specificity. Recently, Vettore et al. described the so-called 'Pink test' as an easy method with the highest reproducibility and sensitivity. Herein, we present our experience with the 'Pink test' in the diagnosis of 16 previously diagnosed hereditary spherocytosis patients comparing the results with those obtained in 96 healthy controls, 41 beta-thalassaemias, 9 autoimmune haemolytic anaemias, 8 chronic hemoproliferative syndromes and 2 patients with pyruvate kinase deficiency. We also present a modification of the original 'Pink test' in which a small sample of blood (200 microL) obtained by finger-prick (or heel puncture in newborns and infants) is mixed with the hemolyzing solution of the 'Pink test' within the first three hours after blood drawing. Elevated correlation coefficients (r = 0.75-0.96) between both methods have been obtained comparing the percentage of final haemolysis in 25 healthy controls, 21 beta-thalassaemia minor and 9 hereditary spherocytosis patients.

Adult↗
PubMed1996

[The spleen in hereditary spherocytosis].

Hereditary spherocytosis is the most common inherent, autosomal dominant hemolytic anemia. Mild splenomegaly, venostasis and common decrease of while pulp is characteristic for hereditary spherocytosis. Cords are filled with spherocytes, sinuses can be empty or squeezed. Both sinuses and veins include ghost erythrocytes that lost haemoglobin. They are seen light-microscopically in differential interferent contrast. Macrophages are numerous, sinus lining cells are hypertrophic. Erythrophagocytosis is hardly seen by electron microscope. Not all red blood cells are spherocytes. Spherocytes are seen well in electronmicroscopy. We did not observed transition of erythrocytes through sinus walls. In certain circumstances lots of ferritin is seen both intra and extracytoplasmically. Iron accumulation in cords can result in their fibrosis.

Humans↗
PubMed1993

Open heart operation in patients suffering from hereditary spherocytosis.

Hereditary spherocytosis is a clinically heterogeneous, genetically determined red blood cell membrane disorder resulting in hemolytic anemia. Structural or functional disorders of the cytoskeletal proteins result in the formation of spherocytes, which lack the strength, durability, and flexibility to withstand the stresses of the circulation. This problem can be accentuated by the deleterious effects of the heart-lung machine. Three patients with hereditary spherocytosis underwent open heart operation with no deaths and no serious complications resulting from the hematologic defect. Splenectomy is recommended, although not essential, before a cardiac operation, and mechanical valves should perhaps be avoided.

Aged↗
PubMedDate not supplied

Hereditary spherocytosis.

Hereditary spherocytosis is a congenital haemolytic anaemia due to defect in spectrin-a RBC membrane protein and is transmitted as autosomal dominant. Due to this defect there is presence of characteristic spherical cell in peripheral blood smear and osmotic fragility is increased. Haemolytic anaemia, reticulocytosis, jaundice and splenomegaly are present. This article reports a case of a 9 year old boy who presented with a history of prolonged jaundice since the age of 4 years and recurrent pain in the right upper quadrant of abdomen. Clinical examination revealed jaundice, enlarged liver and marked splenomegaly. Investigations confirmed the diagnosis of hereditary spherocytosis by the presence of spherocytes in blood smear, raised reticulocytes and increased osmotic fragility. The patient was subjected to splenectomy after vaccination against coccobacillus and was discharged after proper advice and on post splenectomy antibiotic prophylaxis.

Anti-Bacterial Agents↗
PubMed2006

[Molecular mechanism of hereditary spherocytosis].

Hereditary spherocytosis (HS) is a common inherited anaemia in northern Europe characterized by the presence of spherocytic red cells and by heterogeneous clinical presentation, and heterogeneous molecular basis and inheritance. The primary molecular defects reside in the red blood cell membrane, particularly in proteins involved in the vertical interactions between the membrane skeleton and the lipid bilayer. Defects in these interactions lead to the loss of red cell surface area and to the spheroidal shape of the erythrocyte in particular loss of the membrane elasticity and mechanical stability. Severe HS is often associated with a substantial reduction of, and (or) dysfunction of, the affected membrane protein(s). Hereditary spherocytosis stems from mutations in one of the genes encoding ankyrin-1 (ANKI), alpha spectrin (SPTA1) and beta spectrin (SPTB), the anion exchanger 1 (SLC4A 1), and protein 4.2 (EPB42). Inheritance of HS is usually (75%) autosomal, dominant. Recessive and nondominant cases are mostly found in HS associated with ANK1, SPTA1 and SPTB genes.

Alleles↗
PubMed1993

Combined ankyrin and spectrin deficiency in hereditary spherocytosis.

Hereditary spherocytosis is characterized by a reduced spectrin content of the erythrocytes. However, the underlying primary defect remains unclear in the majority of cases. Genetic studies have revealed a linkage to the gene for ankyrin in some families. By means of ELISA we measured the ankyrin, spectrin, and band-3 contents in erythrocytes of 45 patients with typical spherocytosis. They were classified as having mild or moderate spherocytosis, according to clinical severity. Sixteen patients with mild spherocytosis showed slight reductions of ankyrin and spectrin contents. In contrast, 29 patients with moderate spherocytosis exhibited a clear reduction of both ankyrin and spectrin to about 60% of normal. Band 3 and lipid phosphorus, as measures for membrane surface area, were only slightly reduced to 85%. Our results, together with the molecular genetic data indicating the linkage between spherocytosis and the gene for ankyrin, suggest an ankyrin defect or deficiency as the primary lesion in most cases of spherocytosis.

Adolescent↗
PubMedDate not supplied

Partial deficiency of erythrocyte spectrin in hereditary spherocytosis.

Hereditary spherocytosis (HS) is a common, clinically heterogeneous haemolytic anaemia in which the primary erythrocyte defect is believed to be some abnormality in the spectrin-actin membrane skeleton, leading to loss of surface membrane. Recessively inherited spectrin deficiency with extreme erythrocyte fragility and spherocytosis has been identified in certain mutant mice and two severely anaemic humans. Although suspected, deficiency of spectrin has not been demonstrated in less severe forms of human HS. We not report the quantitation of erythrocytes spectrin by radioimmunoassay. We found that normal erythrocytes contained 240,000 copies of spectrin heterodimer, whereas erythrocytes from 14 patients with a variety of types of HS were all partially deficient in spectrin (range 74,000-200,000 copies), the magnitude of the deficiency correlating with the severity of the disease. Spectrin deficiency of varying degrees is common in HS and probably represents the principal structural defect leading to loss of surface membrane.

Erythrocytes↗
PubMed1996

Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis.

Hereditary spherocytosis (HS) is the most common inherited haemolytic anaemia in Northern Europeans. The primary molecular defects reside in the red blood cell (RBC) membrane, particularly in proteins that link the membrane skeleton to the overlying lipid bilayer and its integral membrane constituents. Ankyrin-1 is the predominant linker molecule. It attaches spectrin, the major skeletal protein, to the cytoplasmic domain of band 3, the RBC anion exchanger. Two-thirds of patients with HS have combined spectrin and ankyrin-1 deficiency; deficiency of band 3 occurs in about 15 to 20% (ref.1). These data suggest that ankyrin-1 or band 3 defects may be common in HS. To test this we screened all 42 coding exons plus the 5' untranslated/promoter region of ankyrin-1 and the 19 coding exons of band 3 in 46 HS families. Twelve ankyrin-1 mutations and five band 3 mutations were identified. Missense mutations and a mutation in the putative ankyrin-1 promoter were common in recessive HS. In contrast, ankyrin-1 and band 3 frameshift and nonsense null mutations prevailed in dominant HS. Increased accumulation of the normal protein product partially compensated for the ankyrin-1 or band 3 defects in some of these null mutations. Our findings indicate that ankyrin-1 mutations are a major cause of dominant and recessive HS (approximately 35 to 65%), that band 3 mutations are less common (approximately 15 to 25%), and that the severity of HS is modified by factors other than the primary gene defect.

Ankyrins↗
PubMed2000

The diagnosis and management of hereditary spherocytosis.

Hereditary spherocytosis (HS) is relatively common in Caucasian populations; most individuals have mild or only moderate disease. There is commonly a family history and a typical clinical and laboratory picture so that the diagnosis is usually easily made without additional laboratory tests. Atypical cases may require measurement of membrane proteins and molecular genetics to clarify the nature of the membrane disorder. It is particularly important to rule out stomatocytosis because splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 and with appropriate counselling about the risk of infection. In all cases careful dialogue between physician, child and the family is essential. Laparoscopic surgery can result in shorter hospital stay and less pain.

Erythrocyte Membrane↗
PubMed1994

Erythrocyte membrane protein alterations underlying clinical heterogeneity in hereditary spherocytosis.

Hereditary spherocytosis (HS) is a very heterogenous condition both at clinical and biochemical level. To establish the relationship between these aspects we performed a clinical and biochemical study in 87 Italian HS subjects. Patients were divided into three groups based on clinical severity (mild, typical and severe) and into five subgroups based on specific membrane abnormalities identified by polyacrylamide gel electrophoresis (isolated spectrin deficiency, spectrin deficiency combined with mild ankyrin reduction, spectrin deficiency combined with severe ankyrin reduction, band 3 reduction and isolated protein 4.2 reduction). We were not able to assess any alteration in six HS patients. A good correlation between clinical HS forms and membrane protein defects is shown. We conclude that erythrocyte membrane analysis should be carried out after diagnosis of HS in order to predict the clinical course of the disease.

Adolescent↗
PubMed2004

Guidelines for the diagnosis and management of hereditary spherocytosis.

Hereditary spherocytosis (HS) is a heterogeneous group of disorders with regard to clinical severity, protein defects and mode of inheritance. It is relatively common in Caucasian populations; most affected individuals have mild or only moderate haemolysis. There is usually a family history, and a typical clinical and laboratory picture so that the diagnosis is often easily made without additional laboratory tests. Atypical cases may require measurement of erythrocyte membrane proteins to clarify the nature of the membrane disorder and in the absence of a family history, occasionally molecular genetic analysis will help to determine whether inheritance is recessive or non-dominant. It is particularly important to rule out stomatocytosis where splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 years and with appropriate counselling about the infection risk. In all cases careful dialogue between doctor, patient and the family is essential. Laparoscopic surgery, when performed by experienced surgeons, can result in a shorter hospital stay and less pain.

Folic Acid↗
PubMed1991

Current problems in haematology. 2: Hereditary spherocytosis.

Hereditary spherocytosis is a relatively common haematological disorder and will be encountered by all haematologists. The abundance of new information, dealing principally with molecular and genetic aspects of pathophysiology, is beginning to have implications for its investigation and management. While these advances have not yet exerted a large influence at therapeutic level, the promise of such advents as prenatal diagnosis make this an exciting field to watch.

Erythrocyte Membrane↗
PubMed1967

Membrane lipid depletion in hyperpermeable red blood cells: its role in the genesis of spherocytes in hereditary spherocytosis.

Hereditary spherocytosis (HS) red cells lose membrane lipids excessively during incubation in vitro. Individual phosphatides as well as cholesterol are lost in proportion to their content in membranes, suggesting that fragments of membrane are removed. Supplementation of HS red cells with glucose during incubation has no consistent protective effect, whereas diminishing the excessive sodium flux through these cells by suspending them in either sodium-free or hypertonic media prevents membrane fragmentation. The characteristic excessive increase in osmotic fragility which occurs in incubated HS red cells results both from inordinate accumulation of intracellular sodium ions which produces osmotic swelling, and from depletion of surface material which generates microspherocytosis. Inhibiting both of these processes by incubating HS red cells in sodium-free media completely prevents increases in osmotic fragility despite prolonged incubation. Normal red cells rendered hyperpermeable to cations by exposure either to n-butanol or to inhibitors of membrane sulfhydryl groups, lose membrane lipid upon incubation in a similar fashion to untreated HS red cells; perfectly smooth microspherocytes, akin to those seen in HS, are thereby generated.I conclude that depletion of membrane lipids in HS which leads to microspherocytosis is correlatable with the excessive cation flux and possibly to the stimulated metabolism of acidic phosphatides in these red cells. It is suggested that this relation is derived from the fact that these phosphatides are in some way involved in maintaining the proper alignment of repeating membrane lipoprotein units, and that this function is adversely affected when these molecules are turning over more rapidly in response to increased cation flux.

Benzoates↗
PubMed1988

Reductions of erythrocyte membrane viscoelastic coefficients reflect spectrin deficiencies in hereditary spherocytosis.

Hereditary spherocytosis is a common hemolytic anemia associated with deficiencies in spectrin, the principal structural protein of the erythrocyte membrane-skeleton. We have examined 20 different individuals from 10 spherocytosis kindreds and 2 elliptocytosis kindreds to determine the effects of different levels of spectrin deficiency on the viscoelastic properties of the erythrocyte membrane. Micropipettes were used to perform single-cell micromechanical measurements of approximately 1,000 individual cells to determine the membrane elastic shear modulus, the apparent membrane bending stiffness, and whole cell recovery time constant for the different cell populations. The membrane viscosity was calculated by the product of the shear modulus and the recovery time constant. Results show correlation between the fractional reduction in shear modulus and the fractional reduction in spectrin content (determined by spectrin radioimmunoassay) and spectrin density (determined by the ratios of spectrin to band 3 on electrophoresis gels) suggesting that membrane shear elasticity is directly proportional to the surface density of spectrin on the membrane (P less than 0.001). The apparent membrane bending stiffness is also reduced in proportion to the density of spectrin (P less than 0.001). The membrane viscosity is reduced relative to control (P less than 0.001), but the nature of the relationship between spectrin density and membrane viscosity is less clearly defined. These studies document striking relationships between partial deficiencies of erythrocyte spectrin and specific viscoelastic properties of the mutant membranes.

Elasticity↗
PubMed2000

Abnormalities of erythrocyte membrane proteins in Korean patients with hereditary spherocytosis.

Hereditary spherocytosis (HS) is a common inherited erythrocyte membrane disorder characterized by chronic hemolytic anemia. Clinical manifestations and biochemical abnormalities of HS are heterogeneous. In this study, we investigated erythrocyte membrane protein defects in 27 Korean HS cases. Utilizing both the Fairbanks system and the Laemmli system, sodium dodecyl sulfate polyacrylamide gel electrophoresis of erythrocyte membrane proteins was performed. Proteins were stained with Coomassie brilliant blue and gels were scanned using a densitometer. We detected spectrin deficiency in 7.4% of cases (2/27), ankyrin deficiency in 29.6% (8/27), combined spectrin and ankyrin deficiency in 3.7% (1/27), band 3 deficiency in 11.1% (3/27) and protein 4.2 deficiency in 14.8% (4/27). Membrane protein deficiencies were not observed in nine cases (33.3%, 9/27). Members of two of seven families tested showed the same protein defects as the proband. Ankyrin deficiency alone and combined with spectrin deficiency accounted for 33.3% of cases (9/27), and they were the most common biochemical defects in Korean HS cases. Protein 4.2 deficiency caused HS more frequently in Koreans than in Caucasians.

Anion Exchange Protein 1, Erythrocyte↗