1/39. Inherited protein c deficiency, protein s deficiency and hyperhomocysteinaemia in a patient with hereditary spherocytosis.We report a family with hereditary spherocytosis in whom there is, in addition, a cluster of genetic predispositions to thrombosis. Although inherited prothrombotic abnormalities are prevalent in the general population, the likelihood of this combination of abnormalities being found in a single family is extremely low. The management of such high risk individuals is discussed.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/39. Frequency of very late fatal sepsis after splenectomy for hereditary spherocytosis: impact of insufficient antibody response to pneumococcal infection.Very late sepsis in splenectomized patients with hereditary spherocytosis has been seen rarely up to now; the frequency and the immunodeficiency causing it are largely unknown. Within the past 7 years we have learned of four cases of sepsis or meningitis (three fatal) in adult patients with hereditary spherocytosis who had been splenectomized years earlier. The estimated frequency of very late postsplenectomy infections is 0.69 cases of sepsis or meningitis in 1000 patient-years (0.46 deaths in 1000 patient-years). Pneumococci were proven in two patients. The surviving patient showed low antibody titers against pneumococcal serotypes even after pneumococcal meningitis and subsequent vaccination. There have been several reports of an insufficient response to pneumococcal vaccination in patients with severe infections. We recommend determination of pneumococcal antibody titers after immunization in every splenectomized patient: Nonresponders to vaccination may be at high risk for overwhelming postsplenectomy infection. Our data demonstrate that there is a lifelong risk for severe postsplenectomy infections and therefore the lasting need for immediate antibiotic therapy in any case with sudden onset of high fever.- - - - - - - - - - ranking = 0.125keywords = deficiency (Clic here for more details about this article) |
3/39. Coinheritance of two alpha-spectrin gene defects in a recessive spherocytosis family.We studied a recessive hereditary spherocytosis (HS) family from norway in which all four children had haemolytic spherocytosis while spectrin (Sp) deficiency was detected in the proband. Molecular analysis demonstrated that all affected children had inherited the low expression alpha-Sp allele LEPRA (Low Expressed PRAgue) from the father. Haplotyping with a polymorphic dinucleotide repeat for the alpha-Sp gene (alphaVNTR) located in the 3' untranslated region of mRNA showed that all recessive children had inherited the same maternal alpha-spectrin allele. The paternal Sp-alphaLEPRA allele was found in cis of the polymorphic alpha-Sp Bughill allele (alphaBH) characterized by the A970D point mutation in the Sp alpha-chain. This mutation was identified on two-dimensional electrophoresis of Sp tryptic digests as an acidic shift of the alphaII tryptic domains (spots alphaIIa). Analyses of the relative expression of the paternal alpha-Sp Bughill polymorphism in the proband showed that the product of the maternal alpha-Sp gene is almost completely absent from the mature erythrocyte membrane. Comparative analysis between alphaVNTR PCR-amplified from genomic dna and from cDNA showed that the maternal low expression alpha-Sp allele is associated with a decreased amount of mRNA. Results from molecular and biochemical studies showed that all the affected children of this family are compound heterozygous for two different low expression alpha-Sp alleles: an uncharacterized defective alpha-Sp allele on the maternal side and an alphaLEPRA allele tagged by the alphaIIa polymorphism on the paternal side.- - - - - - - - - - ranking = 0.125keywords = deficiency (Clic here for more details about this article) |
4/39. Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III.Hereditary spherocytosis (HS) is an inherited haemolytic anaemia, characterized by spheroidal, osmotically fragile red blood cells. This disorder exhibits heterogeneity in terms of both clinical severity and underlying molecular defect. We have studied a South African Cape Coloured individual with severe HS owing to a band 3 deficiency caused by two mutations, occurring in trans, in the band 3 gene: a novel variant that we have designated band 3 Cape Town and a previously described mutation, band 3 Prague III. Analysis of erythrocyte membrane proteins indicated a deficiency of both band 3 and protein 4.2, as well as a decreased functional capacity of band 3 to transport anions. Band 3 Cape Town is defined by a GAG-->AAG point mutation at codon 90, substituting a glutamic acid with a lysine in the cytoplasmic domain of the molecule, while band 3 Prague III is a codon 870 CGG-->TGG point mutation, replacing an arginine with a tryptophan in the transmembrane region of band 3. mRNA is transcribed from both mutant alleles, implying that mutant proteins are synthesized, but are either degraded prior to membrane incorporation or insertion is impaired. We conclude that the combination of these two mutations exacerbated the clinical presentation of the proband.- - - - - - - - - - ranking = 0.25keywords = deficiency (Clic here for more details about this article) |
5/39. beta-spectrin Sao PauloII, a novel frameshift mutation of the beta-spectrin gene associated with hereditary spherocytosis and instability of the mutant mRNA.Hereditary spherocytosis (HS) is a common inherited anemia characterized by the presence of spherocytic red cells. Defects in several membrane protein genes have been involved in the pathogenesis of HS. beta-spectrin-related HS seems to be common. We report here a new mutation in the beta-spectrin gene coding region in a patient with hereditary spherocytosis. The patient presented acanthocytosis and spectrin deficiency and, at the dna level, a novel frameshift mutation leading to HS, i.e., a C deletion at codon 1392 (beta-spectrin Sao PauloII), exon 20. The mRNA encoding beta-spectrin Sao PauloII was very unstable and the mutant protein was not detected in the membrane or in other cellular compartments. It is interesting to note that frameshift mutations of the beta-spectrin gene at the 3' end allow the insertion of the mutant protein in the red cell membrane, leading to a defect in the auto-association of the spectrin dimers and consequent elliptocytosis. On the other hand, beta-spectrin Sao PauloII protein was absent in the red cell membrane, leading to spectrin deficiency, HS and the presence of acanthocytes.- - - - - - - - - - ranking = 0.25keywords = deficiency (Clic here for more details about this article) |
6/39. Extramedullary hematopoiesis in hereditary spherocytosis deficient in ankyrin: a case report.Hereditary spherocytosis (HS) is a common inherited hemolytic anemia due to red cell membrane defects. Extramedullary hematopoiesis is a compensatory response to insufficient bone marrow blood cell production. The preferred sites of extramedullary hematopoietic involvement are the spleen, liver, and lymph nodes, but in HS the posterior paravertebral mediastinum is also commonly involved. A nonsplenectomized 74-year-old man with mild HS, with primary deficiency in ankyrin, was found by magnetic resonance imaging to have thoracic paravertebral hematopoietic masses. The patient showed high serum levels of erythropoietin, which may have played a role in the development of extramedullary hematopoietic masses through a continuous hematopoietic stimulus to erythroid cells in the propositus. The long-standing history of respiratory infections and of hypoxia in the propositus may have been an additional etiological factor.- - - - - - - - - - ranking = 0.125keywords = deficiency (Clic here for more details about this article) |
7/39. Study of a kindred with hereditary spherocytosis and glyceraldehyde-3-phosphate dehydrogenase deficiency.A patient with hereditary spherocytosis (HS) was found to have glyceraldehyde-3-phosphate dehydrogenase (G3PD) deficiency by electrophoresis of the isolated red cell membranes on polyacrylamide gels with sodium dodecyl sulfate (PAGE SDS) as demonstrated by a diminished band 6 (G3PD) and confirmed by specific enzyme assay. Thirteen members of his family were studied: four were normal, two had HS alone, three had G3PD deficiency alone, and four had both HS and G3PD deficiency. G3PD deficient kindred members were probably heterozygous, since their red cell enzyme, while qualitatively normal, was present in half normal amounts. The G3PD deficiency alone was asymptomatic, and there was no evidence that the combination of HS with G3PD deficiency increased the clinical severity of the disease. However, G3PD deficiency, when combined with HS, was associated with an increase in protein band 4.5 on PAGE SDS. This band was also increased by incubation of normal red cells without glucose, and appeared to be a protein absorbed to the membrane as a consequence of metabolic stress. Hence, red cells with the combined abnormalities of both HS and G3PD deficiency showed signs of the exceptional metabolic stress to which they were exposed.- - - - - - - - - - ranking = 1.375keywords = deficiency (Clic here for more details about this article) |
8/39. Hereditary spherocytosis (HS) due to loss of anion exchange transporter.BACKGROUND. Hereditary spherocytosis encompasses a heterogenous group of inherited disorders due to alteration of r.b.c. surface/volume ratio. spectrin deficiency is the most common observed defect. We analyzed a case of HS associated with band 3 deficiency without spectrin reduction. methods. In the study of a family originating from southern italy, we show that a 20% deficiency of band 3 with normal spectrin content may be responsible for dominantly inherited hereditary spherocytosis (HS). The proband is a 12 years old girl consulting for jaundice, chronic anaemia and splenomegaly. Her mother had a similar haematologic phenotype. RESULTS. Electrophoretic analysis of erythrocyte membrane proteins showed a deficiency in band 3 protein. Band 3 protein chymotryptic fragments, deglycosylated band 3, and its isolated cytoplasmic domain, all displayed normal electrophoretic migrations. Furthermore, the tryptic peptides profile of the cytoplasmic domain of the protein did not demonstrate any abnormality, nor did the amino acid composition of the peptides. Analysis of the membrane proteins during erythrocyte ageing, evaluated in density-fractionated red cells, showed that band 3 content was normal in the lighter fraction, whereas in the denser fraction band 3 deficiency was more pronounced than in membranes from non fractionated red blood cells. CONCLUSIONS. This case describes HS due to anion exchange transporter deficiency. Our results on fractioned red cells support the hypothesis that the defect was probably due to a band 3 protein loss during cell ageing and not to a primitive quantitative defect.- - - - - - - - - - ranking = 0.75keywords = deficiency (Clic here for more details about this article) |
9/39. Homozygosity for dominant form of hereditary spherocytosis.A 6-month-old male infant with hereditary spherocytosis (HS) who was the first child of a cousin marriage is presented. The patient had splenomegaly and severe anaemia. Examination of the peripheral blood smear revealed spherocytes and the osmotic fragility of red blood cells was greatly increased. physical examination of the parents revealed that both parents had mild anaemia, jaundice and splenomegaly. Their peripheral blood smears showed spherocytes and a few acanthocytes. osmotic fragility of red blood cells of both parents were increased. Red cell membrane electrophoresis indicated a deficiency of ankyrin in the propositus; mild deficiency was also detected in both parents. Electrophoretic patterns of red cell membrane proteins suggested that the child was homozygous for the dominant form of HS associated with ankyrin deficiency, while both parents had the simple dominant form of the disease. Red blood cell transfusions were given to the patient starting at the age of 1 month until splenectomy was performed at the age of 1 year that resulted in complete haematological response. This observation indicates that homozygosity for dominant type of HS associated with ankyrin deficiency is life compatible and splenectomy may cure the anaemia.- - - - - - - - - - ranking = 0.5keywords = deficiency (Clic here for more details about this article) |
10/39. Band 3Tambau: a de novo mutation in the AE1 gene associated with hereditary spherocytosis. Implications for anion exchange and insertion into the red blood cell membrane.Hereditary spherocytosis (HS) is attributed to red blood cell membrane protein defects, caused by mutations in ankyrin, spectrin, band 3 and protein 4.2. In this study, the presence of band 3 mutations was investigated in a patient presenting mild HS and band 3 deficiency. Using single strand conformation polymorphism analysis, a shift in exon 16 of the band 3 gene was found. dna sequencing revealed a point mutation 2102 T>C, changing methionine at position 663 to lysine. The M663K substitution was not found in either the parents or in the siblings, and the restriction fragment length polymorphism analysis of 100 alleles from a random Brazilian population did not reveal this mutation, suggesting that this gene defect is more likely to be a de novo mutation, causing HS. flow cytometry of eosin-5-isothiocyanate (EITC)-labelled erythrocytes showed, in the patient, 54% of band 3 protein content vs. 78% based on the sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, suggesting that flow cytometry is a more sensitive method and may be used as a diagnostic tool in membrane disorders related to band 3 deficiency. The characterisation of novel AE1 mutations is helpful to improve the understanding of the role of band 3 protein in cell physiology.- - - - - - - - - - ranking = 0.25keywords = deficiency (Clic here for more details about this article) |
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