1/26. Mapping of a syndrome of X-linked thrombocytopenia with Thalassemia to band Xp11-12: further evidence of genetic heterogeneity of X-linked thrombocytopenia.X-linked thrombocytopenia with thalassemia (XLTT; Online Mendelian Inheritance in Man [OMIM] accession number 314050) is a rare disorder characterized by thrombocytopenia, platelet dysfunction, splenomegaly, reticulocytosis, and unbalanced hemoglobin chain synthesis. In a 4-generation family, the gene responsible for XLTT was mapped to the x chromosome, short arm, bands 11-12 (band Xp11-12). The maximum lod score possible in this family, 2.39, was obtained for markers DXS8054 and DXS1003, at a recombination fraction of 0. Recombination events observed for XLTT and markers DXS8080 and DXS8023 or DXS991 define a critical region that is less than or equal to 7.65 KcM and contains the gene responsible for the wiskott-aldrich syndrome (WAS; OMIM accession number 301000) and its allelic variant X-linked thrombocytopenia (XLT; OMIM accession number 313900). Manifestations of WAS include thrombocytopenia, eczema, and immunodeficiency. In WAS/XLT the platelets are usually small, and bleeding is proportional to the degree of thrombocytopenia. In contrast, in XLTT the platelet morphology is normal, and the bleeding time is disproportionately prolonged. In this study no alteration in the WAS gene was detected by Northern blot or Western blot analysis, flow cytometry, or complimentary dna dideoxynucleotide fingerprinting or sequencing. As has been reported for WAS and some cases of XLT, almost total inactivation of the XLTT gene-bearing x chromosome was observed in granulocytes and peripheral blood mononuclear cells from 1 asymptomatic obligate carrier. The XLTT carrier previously found to have an elevated alpha:beta hemoglobin chain ratio had a skewed, but not clonal, X-inactivation pattern favoring activity of the abnormal allele. Clinical differences and results of the mutation analyses make it very unlikely that XLTT is another allelic variant of WAS/XLT and strongly suggest that X-linked thrombocytopenia mapping to band Xp11-12 is a genetically heterogeneous disorder.- - - - - - - - - - ranking = 1keywords = splenomegaly (Clic here for more details about this article) |
2/26. beta-thalassemia intermedia caused by compound heterozygosity for Hb Malay (beta codon 19 AAC-->AGC; asn-->Ser) and codons 41/42 (-CTTT) beta(0)-thalassemia mutation.We report a case of beta-thalassemia intermedia caused by compound heterozygosity for hemoglobin (Hb) Malay and codon 41/42 (-CTTT) beta(0)-thalassemia mutation in a 38-year-old Chinese woman. This patient has long-standing anemia with a baseline Hb level of around 70 g/L. She worked as a full-time cashier and had not required regular blood transfusions. Nevertheless, she had splenomegaly necessitating splenectomy, cholelithiasis, and iron overload. This case illustrates the varied phenotypic expression associated with compound heterozygosity for Hb Malay and other beta-thalassemia mutations. Since Hb Malay migrates as Hb A on electrophoresis and chromatography, this variant Hb mutation ought to be included in the differential diagnosis for beta-thalassemia major or intermedia patients of Southeast Asian descent who are reported to have Hb A on the basis of Hb analysis. The possible presence of this mutation should also be considered in appropriate cases for genetic counseling in couples at risk of conceiving fetuses with beta-thalassemia major or intermedia.- - - - - - - - - - ranking = 1keywords = splenomegaly (Clic here for more details about this article) |
3/26. Hb Leslie, an unstable hemoglobin due to deletion of glutaminyl residue beta 131 (H9) occurring in association with beta0-thalassemia, HbC, and HbS.A new unstable hemoglobin, Hb Leslie, has been observed in three generations of a georgia family. The propositus, a 42-yr-old black veteran with hemolytic anemia and splenomegaly, has a hemoglobin variant with an electrophoretic mobility similar to that of hemoglobin F. The variant comprises about 85% of the total hemoglobin and was isolated by chromatography. Chemical analysis has identified the abnormality as a deletion of the glutaminyl residue in position 131 (H9) of the beta-chain. Deletion of this critical residue which participates in the alpha1beta1 contact causes decreased stability of the hemoglobin without significant changes in functional properties or morphologic abnormalities in the erythrocyte. family studies revealed hemoglobin Leslie occurring in combination with beta0-thalassemia, HbS, and HbC. All persons with the various Hb Leslie combinations, including the propositus, have no clinical manifestations other than anemia. In some the anemia is fully compensated. There is no history of drug-associated hemolysis.- - - - - - - - - - ranking = 1keywords = splenomegaly (Clic here for more details about this article) |
4/26. Hypertransfusion: a successful method of treatment in thalassemia intermedia patients with spinal cord compression secondary to extramedullary hematopoiesis.SUMMARY OF BACKGROUND DATA: Extramedullary hematopoiesis is a common compensatory phenomenon to chronic hemolytic anemias including thalassemia. Several sites can be involved including the liver, the spleen, the lymph nodes, and other less common locations. spinal cord compression may result in the rare cases wherein the hematopoietic develops intraspinally. Treatment of such conditions still is controversial. OBJECTIVE: This article reviews the literature and reports two cases of thalassemia intermedia involving patients who presented with neurologic symptoms after acute spinal cord compression secondary to extramedullary hematopoiesis. methods: The diagnosis was established by magnetic resonance imaging. Hypertransfusion therapy was used as our first-line treatment method. RESULTS: Complete neurologic recovery was achieved. Improvement in the neurologic status started as soon as the first week of treatment. CONCLUSIONS: Clinical awareness is important for early diagnosis and prevention of irreversible neurologic complications in such cases. magnetic resonance imaging is the radiologic method of choice for diagnosing extramedullary hematopoietic masses and for delineating the extent of spinal cord involvement. Hypertransfusion seems to be a promising treatment method that should be recommended as a first-line approach or as an adjuvant therapy to other methods.- - - - - - - - - - ranking = 0.014161854358584keywords = spleen (Clic here for more details about this article) |
5/26. Hb Bristol-Alesha presenting thalassemia-type hyperunstable hemoglobinopathy.Hemoglobin (Hb) Bristol-Alesha is caused by a GTG --> ATG mutation at codon 67 in the Hb beta chain, resulting in abnormal beta globin chains with mutated molecules from normal beta67 valine (Val) to beta67 methionine (Met) or beta67 aspartate (Asp). We describe a Japanese child with this rare hemoglobinopathy and a very unstable Hb molecule phenotype. The diagnosis of hemolytic anemia was made when the patient was 6 months of age. Development of marked splenomegaly necessitated red blood cell transfusions twice a month. After splenectomy when the patient was 4 years of age, laboratory findings of hemolytic anemia became more prominent. Specific abnormal Hb molecules initially were not detected, and the alpha/beta globin synthesis ratio was abnormal at 2.22. After splenectomy, we identified the presence of abnormal beta-globin chains with a beta67Val:beta67Met:beta67Asp molecule ratio of 74:11:15. We speculate that the high fraction of the beta67Met molecule in this patient, compared with that in previously reported cases, caused extreme Hb instability, which resulted in thalassemic hyperunstable hemoglobinopathy and very severe clinical findings.- - - - - - - - - - ranking = 1keywords = splenomegaly (Clic here for more details about this article) |
6/26. Haemoglobin Lepore in a Malay family: a case report.A 2-year-old Malay boy was brought to the University Malaya Medical Centre for thalassaemia screening. physical examination revealed thalassaemia facies, pallor, mild jaundice, hepatomegaly and splenomegaly. Laboratory investigations on the patient including studies on the parents lead to a presumptive diagnosis of homozygous Haemoglobin Lepore (Hb Lepore). The aim of this paper is to increase awareness of this rare disorder, this being the first case documented in malaysia in a Malay. The case also demonstrates the need for this disorder to be included in the differential diagnosis of patients presenting clinically like thalassemia intermedia or thalassemia major. Accurate diagnosis would provide information necessary for prenatal diagnosis, proper clinical management and genetic counseling. The clinical, haematological and laboratory features of this disorder are discussed in this paper.- - - - - - - - - - ranking = 1keywords = splenomegaly (Clic here for more details about this article) |
7/26. Monozygotic twins with sickle cell anemia and discordant clinical courses: clinical and laboratory studies.We describe a rare set of monozygotic twins with coexistent sickle cell anemia and alpha-/alpha alpha thalassemia who have asynchronous painful crises of different frequency and severity. Studies include measurements of cell deformability and other hemorheologic tests, cell density distribution, the percentage of irreversibly sickled cells, adherence of red cells to endothelial cells, membrane heme and membrane free iron, calcium containing internal vesicles and serum antioxidants. Results of these studies, including estimates of organ damage (bone, spleen, retina), were similar except for an increase in red cell membrane free iron in the patient with more frequent and severe painful crises. The study supports the concept that non-inherited factors are important contributors to the frequency and severity of painful crises in sickle cell anemia.- - - - - - - - - - ranking = 0.014161854358584keywords = spleen (Clic here for more details about this article) |
8/26. High-dose intravenous immunoglobulin in the management of immune hemolysis in patients with thalassemic disease: factors which determine refractoriness.We report our experience with high dose intravenous immunoglobulin (IVIg) in 3 thalassemic patients who had evidence of possible immune hemolysis. In 2 patients who had serious sepsis, their responses to IVIg were only partial and transient. The other patient who had marked splenomegaly had no evidence of response to IVIg. Both serious infections and large spleen may hamper the effect of IVIg and should be considered before IVIg is to be used in thalassemia.- - - - - - - - - - ranking = 1.0141618543586keywords = splenomegaly, spleen (Clic here for more details about this article) |
9/26. Massive, solitary, intrahepatic, extramedullary hematopoietic tumor in thalassemia.Diffuse compensatory extramedullary hematopoiesis is well known to involve the spleen and liver in certain hematologic disorders. Hematopoietic tumor masses occasionally form and usually occur paraspinally in the posterior mediastinum. A 31-year-old patient with thalassemia is described with a massive, solitary, intrahepatic hematopoietic tumor and a smaller one in the posterior mediastinum. review of the literature indicates that presentation as a large, focal liver lesion is unique. The implications and differential diagnosis are discussed.- - - - - - - - - - ranking = 0.014161854358584keywords = spleen (Clic here for more details about this article) |
10/26. Hemoglobin mississippi (beta 44sercys). Studies of the thalassemic phenotype in a mixed heterozygote with beta -thalassemia. Hemoglobin mississippi (HbMS: beta 44ser cys) has anomalous properties that include disulfide linkages with normal beta-, delta-, gamma-, and alpha-chains, and the formation of high molecular weight multimers. While heterozygotes for HbMS are clinically and hematologically normal and carriers of the beta -thalassemia gene in our family had mild microcytic anemia, the proband with HbMS-beta -thalassemia had a hemoglobin level of 7 g/dl, mean corpuscular volume (MCV) of 68 fl, reticulocytes of 2-6%, HbF of 18%, marked anisocytosis and poikilocytosis, and splenomegaly, all features of thalassemia intermedia. With oxidant stress, her erythrocytes developed multiple dispersed heinz bodies, but HbMS was only mildly unstable. HbMS was susceptible to proteolytic degradation in the presence of ATP. The unexpectedly severe clinical findings in HbMS-beta -thalassemia may result from the proteolytic digestion of HbMS, as well as the excessive alpha-chains characteristic of beta -thalassemia, which combined provide the increment of cellular damage that results in the phenotype of thalassemia intermedia.- - - - - - - - - - ranking = 1keywords = splenomegaly (Clic here for more details about this article) |
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