Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1086 18

Type II congenital dyserythropoietic anaemia (CDA-II or HEMPAS) is an autosomal recessive disorder, representing the most frequent form of congenital dyserythropoiesis. It is characterised by normocytic anaemia, variable jaundice and hepato-splenomegaly. Gallbladder disease and secondary haemochromatosis are frequent complications. We report a case characterised by severe transfusion-dependent anaemia. The proband inherited CDA-II in association with beta-thalassaemia trait. Splenectomy did not abolish the transfusion dependence and this, in association with poor compliance to iron-chelation therapy, prompted us to consider bone marrow transplantation (BMT) from his HLA-identical sibling. The preparative regimen included busulfan, thiotepa and fludarabine, and graft-versus-host disease prophylaxis consisted of cyclosporin A and short-term methotrexate. Engraftment of donor cells was prompt and the post-transplant course uncomplicated. The patient is alive and transfusion-independent 36 months after allograft. This is the first case of severe CDA-II to undergo BMT. Analysis of this pedigree suggests that interaction with beta-thalassaemia enhanced the clinical severity of CDA-II, making BMT an attractive therapy for patients with transfusion dependence.
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PMID:Bone marrow transplantation in a case of severe, type II congenital dyserythropoietic anaemia (CDA II). 1128 93

We describe the molecular and the hematological characteristics of a Korean family with a dominantly inherited beta-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels, and splenomegaly. DNA analysis revealed a CTG (Leu) to CCG (Pro) substitution at codon 114 of the beta-globin gene, that leads to a highly unstable hemoglobin variant, Hb Durham-N.C./Brescia, and this was linked to the beta haplotype V, [+----+-], and framework 2. RNA analysis showed that the proband had comparable levels of mutant and normal beta-mRNA. Translation of the mutant mRNA would give rise to non-functional hyperunstable beta-globin chains, and their degradation would, by placing an additional burden on the proteolytic process of the red blood cell precursors, result in a more severe phenotype.
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PMID:A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-N.C./Brescia. 1130 Mar 52

Eighteen (32%) of 56 children with thalassaemia major, whose ages ranged from 5 to 12 years (mean 8.8), underwent splenectomy at Madina Maternity and Children's Hospital, Saudi Arabia during the period January 1992 to December 1999. This retrospective study was undertaken with the aim of discovering the outcome. The indications for splenectomy were increased transfusion requirements and massive splenomegaly in 17 children and splenic abscess in one. Polyvalent pneumococcal and Haemophilus influenza vaccines were not available and all the children therefore received intramuscular benzathine penicillin prophylaxis prior to surgery and oral penicillin prophylactically afterwards. Post-splenectomy septicaemia did not occur. The mean transfusion requirement reduced from 2 to 4 weeks and the mean pre-transfusion haemoglobin rose from 6 to 9 g/dl. There were no deaths. We conclude that splenectomy can be performed safely in children over 5 years of age with thalassaemia, and that pre- and post-operative penicillin can be given prophylactically in the absence of the recommended vaccines.
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PMID:Splenectomy in thalassaemia major: experience at Madina Maternity and Children's Hospital, Saudi Arabia. 1147 Dec 60

We provide the first description of a homozygote patient for the G-->A substitution in the 5' UTR of the beta-globin gene. The proband was a 17-year-old girl with beta-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7.6 g/dl, Hb A(2) 5.4% and Hb F 14.6% of the total Hb. The Hb A(2) of both parents was 3.5%. The Hb F level in the mother and father were 0.9, 1.2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the beta-gene region of the propositus revealed homozygosity for a G-->A substitution at nucleotide +22 relative to the beta-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G-->A mutation on the expression of beta-gene. Phenotypic expression of this homozygous patient is highly suggestive that G-->A substitution at nt +22 confers a relatively mild (silent) beta(+)-thalassaemia phenotype.
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PMID:beta-Thalassaemia intermedia in a Turkish girl: homozygosity for G-->A substitution at +22 relative to the beta-globin cap site. 1172 17

Homozygosity or compound heterozygosity for beta(0)-thalassemia mutations most commonly results in a transfusion-dependent thalassemia major phenotype. In this report, we describe a 55-year-old male, from Guinea-Bissau, that had been asymptomatic and never transfused until being admitted to hospital with anemia, fever, splenomegaly, and asthenia. Following hospital admission, HIV-2 and Mycobacterium tuberculosis infections were diagnosed, and biochemical and molecular studies revealed homozygosity for beta(0)-thalassemia. At the molecular level, this is the first description of homozygosity for the beta(0)-Black 1,393-bp deletion. In this case, the complete absence of beta-globin gene expression seems to be compensated by an unusually high fetal globin gene expression (Hb F 96%). Beta-globin haplotyping results were compatible with the propositus being homozygous for the Black 2 haplotype and for the absence of the XmnI polymorphism at -158 of (G)gamma-globin gene (-/-). Co-inheritance of genetic factors usually associated with high Hb F levels was not detected. Otherwise, the propositus is a heterozygote for the alpha-globin gene 3.7-kb deletion that is a beneficial modulating factor but not sufficient to explain this extremely mild phenotype. This unusual genotype/phenotype association is discussed in terms of the mechanisms underlying hemoglobin switching during development.
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PMID:Asymptomatic homozygous deletional beta(0)-thalassemia in an African individual. 1211 69

Gene therapy, the replacement of normal human beta- or gamma-globin genes into the hematopoietic stem cells of patients with homozygous beta-thalassemia, is a promising therapy for the future. High-level lineage-specific stable globin expression in transduced cells reinfused into patients in an autologous transplantation setting could be curative, if successful. Previous studies have shown high-level donor chimerism in nonmyeloablated non-thalassemic hosts. We have now studied the conditions for stable long-term engraftment of normal cells into a thalassemia mouse model that lead to high-level donor chimerism and correction of the abnormal phenotype. Thalassemic female mice treated with 0 to 300 cGy whole-body irradiation received transplantations of donor cells harvested from wild-type males. Engraftment of male cells was quantitated by Y-chromosome polymerase chain reaction analysis of blood and marrow progenitors, and changes in hemoglobin levels, red cell morphology, and spleen size were measured at various times posttransplantation. High-level stable donor cell engraftment was achieved in mice given 200 cGy and receiving transplants of 2 x 10(7) or more donor cells. The anemia, abnormal peripheral blood smears, and splenomegaly improved in the thalassemic mice that had successful engraftment. These studies demonstrate that stable and successful levels of engraftment of normal cells can correct the thalassemic phenotype without fully myeloablating the host. This animal model should allow us to test the amount of cytoreduction required and the level of engraftment and beta-globin expression needed in autologous transplantation of beta-globin gene-transduced cells to correct the abnormal phenotype in thalassemic mice, and it may be relevant to human clinical trials, as well.
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PMID:Correction of phenotype in a thalassemia mouse model using a nonmyeloablative marrow transplantation regimen. 1223 71

The presenting symptoms of malignancies like anemia and splenomegaly in thalassemic patients can be overlooked and considered as complications of thalassemia. Our paper deals with a case of large B cell lymphoma with bone marrow involvement in an old lady with thalassemia intermedia. The patient showed complete response after the second cycle of chemotherapy that consists of cyclophosphamide, vincristine, and prednisone (CVP protocol). However, the patient relapsed with bone marrow involvement shortly after (2 weeks) completion of the sixth cycle of chemotherapy, and she was started on monoclonal antibodies Rituximab. On reviewing the literature, only four cases of thalassemia and lymphoma have been reported worldwide, thus making our case the fifth report of this rare combination of diseases.
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PMID:Beta-thalassemia intermedia and non-Hodgkin's lymphoma. 1240 86

Patients affected by beta-thalassemia major require lifelong transfusions because of insufficient or absent production of the beta chain of hemoglobin (Hb). A minority of patients are cured by allogeneic bone marrow transplantation. In the most severe of the hitherto available mouse models of beta-thalassemia, a model for human beta-thalassemia intermedia, we previously demonstrated that globin gene transfer in bone marrow cells is curative, stably raising Hb levels from 8.0-8.5 to 11.0-12.0 g/dL in long-term chimeras. To fully assess the therapeutic potential of gene therapy in the context of a lethal anemia, we now have created an adult model of beta(0)-thalassemia major. In this novel model, mice engrafted with beta-globin-null (Hbb(th3/th3)) fetal liver cells succumb to ineffective erythropoiesis within 60 days. These mice rapidly develop severe anemia (2-4 g/dL), massive splenomegaly, extramedullary hematopoiesis (EMH), and hepatic iron overload. Remarkably, most mice (11 of 13) treated by lentivirus-mediated globin gene transfer were rescued. Long-term chimeras with an average 1.0-2.4 copies of the TNS9 vector in their hematopoietic and blood cells stably produced up to 12 g/dL chimeric Hb consisting of mu alpha(2):hu beta(2) tetramers. Pathologic analyses indicated that erythroid maturation was restored, while EMH and iron overload dramatically decreased. Thus, we have established an adult animal model for the most severe of the hemoglobinopathies, Cooley anemia, which should prove useful to investigate both genetic and pharmacologic treatments. Our findings demonstrate the remarkable efficacy of lentivirus-mediated globin gene transfer in treating a fulminant blood disorder and strongly support the efficacy of gene therapy in the severe hemoglobinopathies.
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PMID:A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta-globin gene transfer. 1248 Jun 89

Splenectomy and cholecystectomy are among the common surgical procedures required to treat complications of sickle-cell disease (SCD), and when performed separately have been shown to be safe and effective. To determine whether cholecystectomy be performed concomitantly with splenectomy (CSC) in these children, we studied a total of 130 children who underwent splenectomy for various hematologic diseases at our hospital. The most common indication was SCD. Ninety-nine patients (86 SCD and 13 sickle-B-thalassemia) underwent splenectomy and 19 (19.2%) (12 males and 7 females, mean age 13.4 years [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]) underwent CSC due to concomitant gallstones, which were asymptomatic in 13 cases. Those with an admission hemoglobin (Hb) of less than 10 g/dl were transfused with packed erythrocytes to increase their Hb to 10-12 g/dl and their hematocrit to 30%-40%. All patients received intravenous hydration the night before surgery at a rate of 1(1/2) times their maintenance rate, which was continued postoperatively until they were able to tolerate adequate oral fluid intake. The indications for splenectomy in those who had CSC were: acute splenic sequestration crisis in 12, splenic abscess in 3, hypersplenism in 2, and massive splenic infarction in 2. Eight patients had massive splenomegaly (spleen weight >1 kg). In 7 cases CSC was done through a left-upper-quadrant (LUQ) transverse incision, in the remaining 12 through an upper midline incision. There was no mortality and only 2 patients developed postoperative complications; a wound infection in 1 and a hematoma in the splenic bed in another. With good perioperative management, CSC is both safe and effective for children with SCD. Both procedures can be performed safely through an upper midline or a LUQ transverse incision, even in the presence of massive splenomegaly.
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PMID:Should cholecystectomy be performed concomitantly with splenectomy in children with sickle-cell disease? 1272 29


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