1/18. Hereditary elliptical stomatocytosis: a case report.The case described demonstrates the development of elliptical stomatocytosis in a neonate and the appearance of elliptical stomatocytes in her mother whose blood film, before delivery, showed elliptocytosis. Further investigations on both individuals indicated a mild haemolytic anaemia. To our knowledge this is the second reported case of elliptical stomatocytosis.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
2/18. Protein 4.1 deficiency and deletion of chromosome 20q are associated with acquired elliptocytosis in myelodysplastic syndrome.We report a case of myelodysplastic syndrome (MDS), associated with prominent elliptocytosis. A 66-year-old male presented with peripheral pancytopenia, and was diagnosed with MDS [refractory anaemia (RA)]. Apart from marked elliptocytosis, dyshaematopoietic features were not evident in his peripheral blood or hypercellular bone marrow. After 18 months, he had progressed to RA with excess blasts in transformation. Analysis of red blood cell membrane proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a reduced quantity of protein 4.1 (30% of control). Deletion of chromosome 20q was identified by conventional cytogenetic analysis and fluorescence in situ hybridization. Marked elliptocytosis, persistent for more than 17 months, decreased strikingly after chemotherapy with idarubicin and Ara-C. These findings suggest that acquired elliptocytosis occurred as an unusual morphological feature of MDS, associated with abnormalities of protein 4.1 and chromosome 20q.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
3/18. Sp alpha I/78: a mutation of the alpha I spectrin domain in a white kindred with HE and HPP phenotypes.Limited tryptic digestion of spectrin (Sp) from seven related individuals manifesting hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP) phenotypes revealed the presence of a novel peptide with a molecular weight of 78 Kd and a concomitant decrease in the alpha I domain (80-Kd peptide), which is the domain involved in the dimer self-association process. Sp from the normal members of this white family exhibited a normal peptide pattern, as compared with controls. The abnormal peptide pattern was associated with a decreased ability of Sp dimer to self-associate. In this kindred in which three generations were available for study, the clinical manifestations were quite variable and ranged from the asymptomatic HE carrier state to hemolytic HE or to severe anemia requiring splenectomy. The severity of the disease appeared to be correlated both with the amount of mutant spectrin (31% to 69%) and with the excess of the Sp dimer found in the membrane (26% to 60%, compared with a normal value of 5.6% /- 2.2%). Partial amino acid sequencing showed that the alpha I/78-Kd peptide resulted from cleavage at lysine residue 10 of the alpha I/80-Kd domain. knowledge of the exon/intron structure of cloned genomic dna encoding the alpha I domain allowed us to amplify in vitro a dna fragment containing the third exon of the alpha-spectrin gene. The amplified fragment was subcloned and sequenced. A G to T transversion was found in the 39th codon (AGT for AGG), which changed the normal arginine to a serine. Hybridization of amplified DNAs with allele-specific oligonucleotides corresponding to the normal and mutant sequences confirmed the presence of the mutation in three other HE members of the family (the propositus mother, brother, and sister).- - - - - - - - - - ranking = 3.8755219040434keywords = hemolytic (Clic here for more details about this article) |
4/18. Clinical and laboratory study of two Caucasian families with hereditary pyropoikilocytosis and hereditary elliptocytosis.Hereditary pyropoikilocytosis (HPP) is a severe, congenital hemolytic anemia occurring almost exclusively in black persons and characterized by extreme red blood cell anisopoikilocytosis. The authors report two unrelated white females with HPP. Both had severe hemolytic anemia at birth, red blood cell morphologic features characteristic for HPP, and increased thermal sensitivity of the red blood cells. Examination of the red blood cell membranes of both patients showed markedly unstable membrane skeletons when subjected to shear stress, spectrin dimer association defects with increased dimers, and partial spectrin deficiency. Limited tryptic digestion of the spectrin molecule from both patients yielded an abnormal pattern with a decrease in the normal 80,000-dalton alpha I domain and a concomitant increase of an abnormal 74,000-dalton peptide (Sp alpha 1/74). One parent and one sibling of one of the patients with HPP had hereditary elliptocytosis (HE) and the Sp alpha 1/74 defect. The other patient with HPP was different from others reported in that both parents were hematologically and biochemically normal. In addition, her daughter had HE and the Sp alpha 1/74 defect.- - - - - - - - - - ranking = 7.7510438080868keywords = hemolytic (Clic here for more details about this article) |
5/18. Double inheritance of an alpha I/65 spectrin variant in a child with homozygous elliptocytosis.Hemolytic anemia with red cell fragmentation, poikilocytosis, and elliptocytosis was discovered in a 6-week-old black infant. Both parents and a brother of the propositus had compensated mild Hereditary Elliptocytosis (HE). Elliptocytosis was prominent in the proband's father with the presence of numerous rod-shaped cells whereas, in the proband's mother, elliptocytosis was less marked and cells were less elongated than in the father. The proband's red cells fragmented at 45 degrees C instead of 49 degrees C for control cells. Both the parents' and brother's red cells fragmented at 47 degrees C. The deformability of the proband's red cells was markedly reduced when measured with the ektacytometer; the red cells of both the proband's parent and brother exhibited an intermediate decrease in red cell deformability. spectrin self-association was defective in the propositus as well as in his parents and brother. Limited tryptic digestion of the proband's spectrin, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), revealed a complete absence of the normal 80,000 dalton alpha I domain and the presence of an abnormal 65,000 dalton peptide. Two-dimensional isoelectric focusing/SDS-PAGE of limited tryptic digests of spectrin from both the proband's parents and brother revealed a decrease in the normal 80,000 alpha I domain and the presence of the 65,000 peptide variant. On the basis of biochemic studies performed on the patients' spectrin, we concluded that the proband had homozygous HE, having inherited the structural defect of spectrin present in a heterozygous state in each of his parents. On a clinical and morphologic level, homozygous HE imitates two other forms of congenital hemolytic anemia associated with a spectrin self-association defect: HE with pycnocytosis in infancy and Hereditary Pyropoikilocytosis. This report emphasizes the importance of confronting clinical and rheological as well as biochemical investigations in studying and discussing different entities.- - - - - - - - - - ranking = 3.8755219040434keywords = hemolytic (Clic here for more details about this article) |
6/18. Modulation of erythrocyte membrane mechanical stability by 2,3-diphosphoglycerate in the neonatal poikilocytosis/elliptocytosis syndrome.To explain the transient anemia and poikilocytosis seen during infancy in hereditary elliptocytosis (HE), we resealed erythrocyte (RBC) ghosts from affected children or their elliptocytic parents with 2,3-diphosphoglycerate (DPG) (0-8 mM), a compound that dissociates membrane skeletons, then measured ghost mechanical stability in the ektacytometer. Without added 2,3-DPG, ghost mechanical stability was subnormal in infantile poikilocytosis (IP) and HE but was even more abnormal in hereditary pyropoikilocytosis (HPP). Addition of 2,3-DPG (2.55 mM) to IP or HE ghosts, decreased their stability to that of HPP ghosts (without 2,3-DPG). Nonphysiological 2,3-DPG levels (6-8 mM) were required to elicit a similar effect in normal ghosts. The data suggest that free 2,3-DPG, present in neonatal RBC as a consequence of diminished binding to HbF, may render HE susceptible to in vivo fragmentation. The developmental switch from fetal to adult hemoglobin, by diminishing available free 2,3-DPG, may explain the abatement of poikilocytosis and hemolytic anemia that accompanies maturation.- - - - - - - - - - ranking = 3.8755219040434keywords = hemolytic (Clic here for more details about this article) |
7/18. A case of elliptocytosis associated with a truncated spectrin chain.A case of haemolytic anaemia with elliptocytosis is described, in which a large part of the smaller (beta) subunit of the spectrin is truncated, and has an apparent molecular weight of about 214 000 compared with about 230 000 for the normal chain. It is shown that this is not a product of adventitious proteolysis during lysis or extraction. At the same time about 35% of the total spectrin in the cells is liberated from the membrane as the dimer (which is present in normal cells to the extent of less than 10%). The truncated (beta') chain appears exclusively in this dimer fraction. The beta'-chain is incapable of phosphorylation by the endogenous cAMP-independent membrane kinase, and it may be inferred that the deleted segment of the chain contains both the spectrin self-association site and the residues normally phosphorylated. The alpha beta'-dimer is active with respect to participation in a ternary complex with its partnering proteins in the membrane cytoskeleton, F-actin and 4.1, confirming that the phosphorylation sites are not involved in the primary interaction with the other cytoskeletal proteins at the network junctions. The spectrin alpha-chain generates the terminal tryptic fragment of molecular weight 80 000 characteristic of normal spectrin, rather than the 74 000 molecular weight peptide derived from the alpha-chain in cases of hereditary elliptocytosis and pyropoikilocytosis, associated with anomalous self-association of spectrin dimer. Membrane cytoskeletons, extracted from the patient's red cells, undergo normal gelation on incubation with cAMP-independent kinase and ATP, and thus do not resemble those derived from hereditary spherocytosis cells. The properties of the anomalous spectrin resemble in most respects that described in a French family by Dhermy et al (1982).- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
8/18. Auto-immune haemolytic anemia complicating infectious mononucleosis in a patient with hereditary elliptocytosis.Auto-immune haemolytic anemia complicating infectious mononucleosis occurred in a patient with hereditary elliptocytosis. A cold antibody of IgM anti-i specificity with narrow thermal amplitude was identified in the serum and the erythrocytes were found to be coated with complement. Significantly excessive erythrophagocytosis was demonstrated in samples of the patient's blood which had been chilled and then incubated at 37 degrees C. The patient recovered spontaneously. The elliptocytosis does not appear to have contributed to the episode of haemolytic anaemia; the other elliptocytic member of the family (her father) had no history and no present evidence of haemolysis.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
9/18. Hereditary pyropoikilocytosis: report of two cases from saudi arabia.Hereditary pyropoikilocytosis is a rare type of congenital hemolytic anemia reported only in American black children. We report the first two occurrences in Saudi children. This is an autosomal-recessive trait as proved by normal parents and two affected children. A pathogenetic and probably causal relationship with apparent elliptocytosis seems clear as three sibs have that condition.- - - - - - - - - - ranking = 3.8755219040434keywords = hemolytic (Clic here for more details about this article) |
10/18. Pernicious anaemia with subacute combined degeneration of cord in a Bangladeshi male.Pernicious anaemia (PA) has previously not been reported from bangladesh. A case is described which had the typical clinical features of PA with subacute combined degeneration of the cord and polyneuropathy. The patient had typical macroovalocytosis, megaloblastic bone marrow and schilling test result in the range of PA. Vitamin B12 level in the serum was markedly reduced. There was rapid clinical and haematological response to vitamin B12 therapy.- - - - - - - - - - ranking = 5keywords = anaemia (Clic here for more details about this article) |
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