21/430. Bilateral pleural effusions in a beta-thalassemia intermedia patient with posterior mediastinal extramedullary hematopoietic masses. Intractable bilateral exudative pleural effusions developed, following systemic sepsis without pulmonary infection, in a beta-thalassemia intermedia patient with longstanding mediastinal hematopoietic masses. The pleura were not infiltrated by hematopoietic cells. Bilateral talc pleurodesis successfully controlled the effusions. ( info) |
22/430. association of unstable hemoglobin variants and heterozygous beta-thalassemia: example of a new variant Hb Acharnes or [beta53(D4) Ala --> Thr]. We report here the functional and structural characterization of Hb Acharnes [beta53(D4) Ala --> Thr], an unstable and electrophoretically silent variant, that was found associated in trans with a beta(0)-thalassemic mutation (IVSI-1 G --> A), in a patient with thalassemia intermedia syndrome. This case is discussed in comparison with other sporadic cases that we have previously investigated, resulting from the co-inheritance of a beta(0)-thalassemic mutation (CD39 C --> T) with two other types of unstable hemoglobins, Hb Koln [beta98(FG5) Val --> Met], and Hb Arta [beta45(CD4) Phe --> Cys]. It may be concluded that, in these associated forms, both the degree of instability of the variant and the altered oxygen binding properties (affecting the degree of tissue hypoxia) are major determinants of their clinical expression. ( info) |
23/430. Severe inclusion body beta-thalassaemia with haemolysis in a patient double heterozygous for beta(0)-thalassaemia and quadruplicated alpha-globin gene arrangement of the anti-4.2 type. We describe a new case of an association of alpha-globin gene quadruplication of the anti-4.2 type with beta(0)-thalassaemia. The patient, a young woman of mixed Brazilian-Portuguese origin, suffered from chronic haemolytic anaemia with splenomegaly. bone marrow supravital staining with brilliant cresyl blue and electron microscopy studies showed large inclusion bodies in about 3% of erythroblasts. Upon immunofluorescent staining these inclusions reacted with a monoclonal antibody to alpha- but not to beta-globin. Analysis of alpha-globin cluster by Southern blotting showed the presence of pathologic fragments specific for the anti-4.2 alpha-globin gene quadruplication. Alpha/beta mRNA ratio was higher than in cases combining alpha-globin triplication and beta(0)-thalassaemia or in cases of beta(0)-thalassaemia heterozygous state alone (18, 14.7 and 10.1 respectively). Our data confirmed the hypothesis that the clinically detectable haemolysis in this beta(0)-thalassaemic patient was due to an unusually high amount of precipitated alpha-globin in erythroid precursors. This considerable excess of alpha-globin chains was due partly to the beta-globin deficit caused by the presence of the beta(0)-thalassaemic gene, but also to the presence of 6 active alpha-globin genes resulting from alpha-globin gene quadruplication in one chromosome. ( info) |
24/430. Characterization of a new polymorphism, IVS-I-108 (T-->C), and a new beta-thalassemia mutation, -27 (A-->T), discovered in the course of a prenatal diagnosis. We report two new substitutions, IVS-I-108 (T-->C) and -27 (A-->T), identified in a couple at risk for beta-thalassemia. One is of Iranian origin and presents with two mutations: a new substitution of T-->C at nucleotide IVS-I-108, which is a silent polymorphism, and a previously described beta-thalassemia mutation at nucleotide -28 (A-->C). The other is from the island of Corsica, the only place in france where beta-thalassemia is endemic. He presents a new substitution of A-->T at nucleotide -27 in the tata box, which was also found in several members of his family with the beta-thalassemia trait. The fetus was found to have inherited both these novel mutations. ( info) |
25/430. hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia. hydroxyurea (HU) and sodium phenylbutyrate (SPB) have been shown to increase fetal hemoglobin (Hb F) levels in patients with thalassemia intermedia. The reported effects of these agents in increasing total Hb, however, have been inconsistent and there have been no studies on the combination of these medications. We describe the clinical response, as determined by increases in total Hb and decreased transfusion needs, in five patients with thalassemia intermedia treated with HU alone or in combination with SPB. All of the patients responded with increased levels of Hb F, but the responses in total Hb varied. Of the five patients, two had a marked response in total Hb in excess of 3 g/dl, two responded modestly with an increase in total Hb of 1-2 g/dl, and one did not respond. Prolonged responses were achieved with low doses of HU (3-10 mg/kg/day) and higher doses were associated with mild reversible hematologic or hepatic toxicity and no further increases in Hb. sodium phenylbutyrate was added to treatment with HU in two patients, but failed to produce an increase in total Hb despite increasing Hb F levels. Of the four patients who responded to HU with an increase in total Hb, all reported symptomatic improvement and three have not required further transfusions. We conclude that low-dose HU therapy in patients with thalassemia intermedia may increase total Hb levels sufficiently to eliminate the need for transfusions. We, therefore, recommend a trial of HU for thalassemia intermedia patients in whom chronic transfusion therapy is being contemplated. ( info) |
| legg-calve-perthes disease is an idiopathic osteonecrosis or avascular necrosis of the capital femoral epiphysis and the associated complications thereof occurring in an immature growing child. The association between osteonecrosis of the femoral head and thrombophilia was postulated by Glueck in 1994. We describe legg-calve-perthes disease associated with protein c deficiency and beta-thalassemia major in two children among a cohort of 79 beta-thalassemia patients treated in our clinic. The association of thrombophilia, aseptic necrosis of the femoral head, and beta-thalassemia has not been previously described in the literature. ( info) |
27/430. Imaging features of focal intrahepatic extramedullary haematopoiesis. The imaging findings of focal intrahepatic extramedullary haematopoiesis (EMH) in a 51-year-old woman with beta-thalassaemia intermedia are described with particular reference to MRI and CT. bone marrow colloid scintigraphy was unhelpful in confirming the diagnosis, which was made from fine needle aspiration. This is the first description of stellate scars occurring in an EMH lesion. A review of the radiological appearances of this rare condition is presented. ( info) |
28/430. Dominant beta-thalassaemia: a highly unstable haemoglobin is caused by a novel 6 bp deletion of the beta-globin gene. Beta-thalassaemia is inherited as an autosomal recessive trait in most families. Particular interest has recently been focused on the molecular pathology of the rare forms with a dominant mode of inheritance. The index patient and her mother, who are described in this report, displayed typical clinical and haematological features of beta-thalassaemia intermedia with significant ineffective erythropoiesis and additional peripheral haemolysis. Molecular analysis demonstrated a heterozygous genotype for a novel 6 bp (TGGTCT) deletion of the beta-globin gene involving codons 33-35. This deletion results in the removal of two valine residues from the beta-globin chain at position 33/34 (B15/B16) and the substitution of the tyrosine residue at position 35 (C1) by an aspartic acid (beta 33-35 [B15-C1] Val-Val-Tyr-->0-0-Asp). According to the index patient's place of birth, this abnormal haemoglobin has been termed Hb Dresden. The stability of the variant and the normal beta-globin chains were similar during the incubation period of in vitro globin chain synthesis analysis. However, Hb Dresden is exquisitely unstable and cannot be detected in the peripheral blood by haemoglobin electrophoresis, high-performance liquid chromatography (HPLC) or isoelectric focusing. This instability can be explained by the vital structural role of the three affected amino acids that, in normal haemoglobin, establish a total of nine intermolecular bonds (five hydrophobic and four polar) at both the alpha1beta1 (alpha2beta2) and the alpha1beta2 (alpha2beta1) interface. ( info) |
29/430. Haematopoietic tissue presenting as a sphenoid sinus mass: case report. We report an incidentally discovered mass in the sphenoid sinus in a patient with beta thalassaemia and sickle-cell disease which proved to be an isolated site of extramedullary haematopoiesis in the skull. ( info) |
| Reproductive failure is common in beta-thalassemia major patients because of endocrine damage resulting from iron overload. Here 3 full-term pregnancies following spontaneous ovulation in 2 splenectomized beta-thalassemia major women are reported. The main echocardiographic parameters, such as left ventricular end-diastolic and end-systolic diameters, fractional shortening and ejection fraction, were within the normal range before pregnancy, but worsened during gestation, and 1 patient developed pre-congestive heart failure. deferoxamine therapy was continued throughout 2 pregnancies, while in the other it was stopped after 8 weeks: no abnormalities were noted in the children. Thanks to the currently applied therapies, an increased number of pregnancies may now be expected in beta-thalassemia major women: it is important to find out more about the pregnancy-related problems and their management in these patients. ( info) |