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 reviewed the results of the Dutch paediatric bone marrow transplant (BMT) program for children receiving HLA-identical BMT for beta-thalassaemia major over an 18-year period. In all, 19 patients underwent a total of 21 transplants in our treatment centre between July 1984 and February 2002. Eight females (age 0.3-12 years; median 5 years) and 11 males (age 0.8-18 years; median 6 years) were included. Information, prospectively collected, included molecular defects, donor genotype, beta/alpha-globin expression rates, serum ferritin levels, hepato-splenomegaly, chelation history, virology screening, liver pathology together with post-transplant outcome inclusive of leucocyte chimerism. In total, 11 patients received standard busulphan/cyclophosphamide (Bu/Cy) conditioning, with or without ATG. Stable engraftment was seen in 5/11 with late rejection occurring in six patients. Of these, two children underwent a second successful SCT. For this group, overall event-free survival (EFS) and disease-free survival (DFS) were 90 (10/11) and 64% (7/11), respectively. The probability of rejection was 55%. Subsequent addition of melphalan to the conditioning regimen resulted in long-term stable engraftment in all patients with an EFS/DFS for this group of 90% (9/10). Treatment-related mortality, irrespective of conditioning, was low at 5% (1/19 patients). Veno-occlusive disease (VOD) occurred in 19% (4/21 transplants) and acute GvHD in 19% (4/21 transplants). Post-BMT beta/alpha synthetic ratio measurement monitored donor erythroid engraftment and predicted rejection with a return to transfusion dependency. Maintained full donor chimerism is indicative of stable engraftment both for leucocyte and erythroid lineages, whereas mixed donor chimerism is not. Our results emphasise the importance of the conditioning regimen and post-transplant chimerism surveillance predictive of rejection or long-term stable engraftment.
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PMID:Paediatric allogeneic bone marrow transplantation for homozygous beta-thalassaemia, the Dutch experience. 1279 87

A family of mixed Indian-Portuguese ancestry is reported in which there is a hereditary persistence of foetal haemoglobin and beta-chain thalassaemia. The propositus, a 17-year-old boy, was found to have a mild haemolytic anaemia characterized by slight splenomegaly, microcytosis, numerous target cells, decreased osmotic fragility, a very high level of foetal haemoglobin (75%), and normal haemoglobin A(2) level. Examination of 12 other members of the family showed the following: Three individuals (father, sister, and nephew) had high levels of foetal haemoglobin (25%) but without other clinical or haematological abnormalities. Two individuals (mother and sister) had the features of thalassaemia trait with increased haemoglobin A(2) and normal levels of foetal haemoglobin. The condition in the propositus appears to be the result of heterozygosity for a gene which is responsible for the hereditary persistence of foetal haemoglobin (high F gene) combined with heterozygosity for a beta-thalassaemia gene and provides further evidence for allelism of these genes. The possible genetic basis for the high F state and beta-chain thalassaemia is discussed.
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PMID:Observations on the high foetal haemoglobin gene and its interaction with the thalassaemia gene. 1386 31

The global health impact of malaria is enormous, with an estimated 300-500 million clinical cases and 1 million annual deaths. In humans, initial susceptibility to infection with Plasmodium species, disease severity and ultimate outcome of malaria (self-healing or lethal) are under complex genetic control. Alleles associated with sickle cell anemia, beta-thalassemia and deficiency in glucose-6-phosphate dehydrogenase have a protective effect against malaria and may have been retained by positive selection in areas of endemic malaria. Likewise, genetic variations in erythrocyte antigens and levels of host cytokines affect type and severity of disease. A mouse model of infection with Plasmodium chabaudi was used to study the genetic component of malaria susceptibility. Segregation analyses in informative F2 crosses derived from resistant C57BL/6J and susceptible A/J, C3H and SJL strains using extent of blood stage replication of the parasite and survival as traits mapped three P. chabaudi resistance (Char) loci on chromosomes 9 (Char1), 8 (Char2) and 17 (Char3, MHC-linked). Recombinant congenic strains AcB55 and AcB61 are unusually resistant to malaria despite carrying susceptibility alleles at Char1 and Char2. Malaria resistance in AcB55 and AcB61 is associated with splenomegaly and constitutive reticulocytosis, is inherited in an autosomal recessive fashion and is controlled by a locus on chromosome 3 (Char4). Sequencing of candidate genes from the Char4 region identified a loss-of-function mutation (269T-->A, resulting in the amino acid substitution I90N) in the pyruvate kinase gene (Pklr) that underlies the malaria resistance in AcB55 and AcB61. These results suggest that pyruvate kinase deficiency may similarly protect humans against malaria.
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PMID:Pyruvate kinase deficiency in mice protects against malaria. 1459 40

Portal vein thrombosis (PVT) following splenectomy is a potentially life-threatening complication, and the true incidence of PVT in splenectomized patients is unknown. The objective of this study was to determine the incidence of symptomatic PVT after splenectomy. The hospital database was searched to identify cases of PVT associated with splenectomy from January 1990 to May 2002. Six hundred eighty-eight patients underwent splenectomy during this period, 321 of them for hematologic diseases. Eleven of the 688 patients had PVT associated with splenectomy, and the charts of these patients were reviewed. Six patients developed PVT after splenectomy. Five had hematologic diseases. Symptoms were abdominal pain (6), ileus (5), fever (3), or diarrhea (2). Diagnosis was confirmed by computed tomography (CT) (4), duplex ultrasonography (1), and magnetic resonance imaging (1). The indications for splenectomy included hemolytic anemia (3), thalassemia (1), and myelofibrosis (1). One patient had an incidental splenectomy during gastrectomy. There were four laparoscopic and two open splenectomies. The median interval between splenectomy and diagnosis of PVT was 40 days (range, 13-741). One patient died of pulmonary embolism. Five of six patients with postsplenectomy PVT had splenomegaly and hemolysis. We conclude that the risk of PVT is higher in patients with hematologic conditions associated with splenomegaly and hemolysis.
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PMID:Portal vein thrombosis following splenectomy: identification of risk factors. 1462 54

Sickle beta-thalassaemia (S beta-thalassaemia) is a condition, which results from coinheritance of a sickle cell gene and a beta-thalassaemia gene. The clinical phenotype depends on the type of beta-thalassaemia gene (beta+ or beta(o)). There are several similarities in clinical and haematological features, which sometimes pose a difficulty in correct diagnosis. A definitive diagnosis is required in order to initiate early supportive treatment in patients with homozygous sickle cell disease (SS disease) and to define the later clinical course. Forty-seven cases of haemoglobin sickle syndrome (HbS syndrome) were studied. The clinico-haematological features and high-performance liquid chromatography (HPLC) results from 17 patients with S beta-thalassaemia were compared with those of SS disease (10 patients). Splenomegaly was more commonly found in patients with S beta-thalassaemia. Among the haematological features, red blood cell counts and HbA2 levels were significantly higher in patients with S beta-thalassaemia, while red cell indices, such as MCV, MCH were significantly lower than those seen SS disease. MCHC, PCV total haemoglobin (Hb), HbS, A and HbF were similar in the two groups.
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PMID:Subclassification of HbS syndrome: is it necessary? 1464 Nov 42

We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.
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PMID:Dominant beta-thalassemia with hemoglobin Hradec Kralove: enhanced hemolysis in the spleen. 1468 90

Efforts have been undertaken to find an alternative approach to packed red cell transfusion (PRCT) in major beta-thalassemia. Augmentation of fetal hemoglobin (HbF) by hydroxyurea (HU) has been reported to be less effective in this condition as compared to sickle cell anemia due to molecular heterogeneity of the former disease. HU efficacy and its relation to Xmn1 polymorphism and IVSII-1 mutation was evaluated in major beta-thalassemics. Forty-five patients, M/F ratio 0.8, aged 6-33 years, received oral HU, 20 mg/kg per day, 4 days per week and daily1 mg folic acid. Thirty-six patients were PRCT dependent (group A) and nine independent (group B). The aim was to stabilize or increase pre-PRCT Hb over 10.0+/-0.5 g/dl and to reduce the need or cease the PRCT in group A and to increase Hb level and curb the ineffective erythropoesis, e.g., splenomegaly, facial bone deformity, in group B. HU was administered for at least 6 months (mean: 9 months) and discontinued in case of response failure. Screening for Xmn1 polymorphism and IVSII-1 mutation was carried out in most patients. In group A, 25 patients have become PRCT independent for a period of 2.5-7.3 years (mean: 4 years). The mean Hb, pre-HU 10.0 and post-HU 10.7 g/dl (range: 8.8-13.7 g/dl), mean serum ferritin pre- and post-HU was1877 and 525 ng/ml. The PRCT requirement was reduced in one patient, and ten patients did not respond. In group B HU has been given over 3.3 years (range: 2.8-4.8 years), Hb increased from 9.3 to 10.4/dl, and there was no tangible progression of ineffective erythropoesis. Responders in both groups expressed more comfort with this regimen. Xmn1 and IVSII-1 (homo- and/or heterozygosis) are relevant markers in most responding patients. Molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological HbF switching by HU.
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PMID:Hydroxyurea in the treatment of major beta-thalassemia and importance of genetic screening. 1472 38

Splenomegaly is a common finding in beta-thalassemia; however, its hemodynamic features and its potential correlations with high output state and hepatic disorders, both also frequent in thalassemia, have not yet been assessed in these patients. Eight beta-thalassemia patients with the indication for splenectomy and no symptoms or signs of heart disease, aged 25.6+/-5.5 years, were studied. Preoperative assessment included hematological profile, liver biology, hepatitis virus serology, and echocardiography. During splenectomy, splenic artery blood flow and splenic vein pressure were directly measured and liver biopsies were taken. Preoperative echocardiographic data were compared with those of 34 healthy controls. The preoperative cardiac index was significantly elevated in patients (4.8+/-1.3 vs 3.4+/-1.1 l/min per m2 in controls, p<0.001). Splenic blood flow, although increased, was not particularly high, being 285+/-56 ml/min or 0.13+/-0.04 ml/min per g of splenic mass, representing 4.1+/-0.9% of total cardiac output (CO). Splenic vein pressure was considerably elevated (29.7+/-5.5 cmH2O). Hepatic fibrosis, iron deposition, and extramedullary foci were found in all eight biopsies. Serology was positive in five of eight cases. beta-thalassemia patients with extensive splenomegaly requiring splenectomy are characterized by high output state, increased splenic blood flow, which probably makes a limited contribution to CO elevation, and portal hypertension, manifest by increased splenic vein pressure and hepatic histopathological abnormalities.
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PMID:Hemodynamic assessment of splenomegaly in beta-thalassemia patients undergoing splenectomy. 1533 97

The Authors report on a 16 year-old girl, of Cambodian descent, who was admitted to the hospital for hematuria. She showed a mild microcytic, hypochromic anemia with a normal iron balance; clinical examination was normal with neither pallor nor icterus nor splenomegaly; electrophoresis of hemoglobin yielded no hemoglobin A, a sligtly increased amount of HbF and a single band with a mobility similar to that of HbA2; the patient showed no evidence of overt increased hemolysis. With the DNA technology a final diagnosis of homozygous hemoglobin E was made. Hemoglobin E is the most common Hb variant among Southeast Asian populations. The Authors discuss on the benign nature of Hb-EE disease, pointing out that the presence of a single HbE gene in combination with that for beta-thalassemia leads generally to a disorder often comparable in severity to that of homozygous beta-thalassemia. With the recent migration of a high number of people from the countries, where HbE is extremely frequent, to the Western world (including Italy), this thalassemia syndrome is now a global health problem; therefore its knowledge is an important diagnostic challenge to all the experts involved in the care of thalassemic patients.
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PMID:[Homozygous hemoglobin-E (Hb-EE) disease]. 1552 16

A rare case of an unusual association of liver hydatidosis (LH) and beta-thalassemia (beta-Thal) was reported. In a 43 year old white man, who has no connection to endemic areas of echinococcosis or beta-Thal (but was operated probably for splenic echinococcus 25 years ago), an intermediate form of beta-Thal according hematologic morphologic, and hemoglobin-electrophoretic criteria was diagnosed. Common and different criteria to another anemias (especially of iron deficiency) was discussed and authors believed that this splenomegaly (as specific sign of hereditary beta-Thal) isn't indication for operation. Conventional X-ray, US, and CT was characteristic for LH, and intraoperative cytology was performed. Correlation to a very interesting and rare analogous case, but of homozygous hemoglobinopathy C was made.
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PMID:[The rare combination of liver echinococcosis and beta-thalassemia]. 1564 37


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