1/6. Phenotypic variability of Filipino beta(o)-thalassemia/HbE patients in indonesia.Three Indonesian patients with identical genotypes, each compound heterozygotes for Filipino beta(o)-thalassemia/HbE, expressed different clinical severities. One patient has mild disease and is transfusion independent, while the other two are severely affected and transfusion dependent. The size of the Filipino beta(o)-globin gene deletion was confirmed to be 45 kb, resolving conflicting values given in the literature. Neither ameliorating genetic factors such as alpha-globin gene deletions or the XmnI restriction site polymorphism at position -158 upstream of the (G)gamma-globin gene, nor differences in beta-globin gene haplotype, explain the phenotypic variation. These observations have implications for the development of antenatal diagnosis in indonesia, as at present it is not possible to give an accurate prediction of severity of phenotype for this common genotype.- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
2/6. Differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia by protein and dna analyses.dna analysis was used to confirm the Hb EE genotype and to differentiate from the possible genotype of Hb E-beta(0)-thalassemia in two Malay patients. The first patient was a 13-year-old Malay girl, whose parents were available for family studies. The second patient was a 69-year-old Malay woman with no living family members. The presence of Hb E in both propositi was confirmed by: (1) its characteristic electrophoretic mobilities on alkaline/acid gels; (2) its chromatographic properties on anion/cation exchangers, and (3) its mildly insoluble properties. However, differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia was challenging in these two cases. In the former, this was because of the possible interactions of the parents' phenotypes; i.e., the mother had a similar phenotype. In the latter, it was due to the lack of any living family members for family studies. In this communication, we present the protein and dna analyses, including data on the use of the restriction enzyme Mnl I, for the definitive diagnosis of the Hb EE genotype in the propositi of these two Malay families.- - - - - - - - - - ranking = 1.2keywords = thalassemia (Clic here for more details about this article) |
3/6. Severe central nervous system thrombotic events in hemoglobin Sabine patient.Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype. Extremely high level of Hb F and rather mild anemia in our patient could be partially explained by the presence of G gamma Xmn I polymorphism. This case of Hb Sabine, unlike all other reported to date, shows extremely severe thromboembolic complications. It is our opinion that the hypercoagulable state described in thalassemia is not the only factor responsible for this specific clinical state. The presence of MTHFR C677T mutation in heterozygous state found in our patient and unstable Hb Sabine molecules could contribute to development of thromboembolic phenomena. However, it remains unclear whether other factors participate in pathogenesis of the disease. In this paper we emphasize different genetic background of father and son both affected with Hb Sabine, but with markedly different severity of the disease.- - - - - - - - - - ranking = 0.2keywords = thalassemia (Clic here for more details about this article) |
4/6. Double heterozygosis for hemoglobin c-beta thalassemia: description of a Spanish family. hemoglobin c-beta thalassemia in a Spanish family.A spanish family is described with two abnormal genes: 1) hemoglobin c in heterozygosis with normal hemoglobin, introduced by the subject's mother, and 2) heterozygotic betathalassemia for which the father is a carrier. In the subject and his sister, both abnormal genes coincide with the presence of hemoglobin c and hemoglobin F, simulating homozygosis for hemoglobin c. The clinical condition shows medium intensity chronic hemolysis. In the subject's brother, mother and grandmother, simple heterozygosis of hemoglobins A-C is seen, with no apparent clinical manifestations. The father shows subjaundice with some acute hemolytic episodes. Hypotheses are discussed which might explain the presence of these hemoglobins in spain.- - - - - - - - - - ranking = 1.8keywords = thalassemia (Clic here for more details about this article) |
5/6. spinal cord compression in thalassemia. Report of 12 cases and recommendations for treatment.Twelve patients with beta-thalassemia/hemoglobin e disease had spinal cord compression. Ten were made and two female, aged 17 to 40 years. The causes of spinal cord compression presumably were extramedullary hematopoietic masses. This was proved by surgery in two cases. In six cases, myelography demonstrated extradural blockade. In the others, the recurrent nature of the paraparesis and the prompt response to deep x-ray therapy were compatible with cord compression by extramedullary hematopoietic masses. Although spontaneous recovery and disappearance of the neurological signs after blood transfusions were observed, these were slow and uncertain. Deep x-ray therapy led to prompt response with more lasting benefit in all cases and is thus recommended as standard treatment for this complication.- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
6/6. Interaction of hemoglobin e and pyrimidine 5' nucleotidase deficiency.A Bangladeshi family is described in which the genes for both hemoglobin e (Hb E) and pyrimidine 5' nucleotidase deficiency are segregating. An individual homozygous for both these conditions has a severe hemolytic anemia, whereas family members who are homozygous for Hb E are asymptomatic and those homozygous for pyrimidine 5' nucleotidase deficiency have the mild hemolytic anemia that is characteristic of this disorder. Globin-chain synthesis experiments have shown that the mechanism underlying the interaction between these two genotypes is a marked decrease in the stability of Hb E in pyrimidine 5' nucleotidase-deficient red blood cells (RBCs). It has also been found that in the enzyme-deficient RBCs in which Hb E is highly unstable, free alpha-chains, though not beta E-chains, acoumulate on the membrane. In view of the increasing evidence that the hemolysis associated with pyrimidine 5' nucleotidase deficiency results not only from an increase in the level of erythrocyte pyrimidines, but also from inhibition of the hexose monophosphate shunt activity in young erythrocytes, it is likely that the marked instability of Hb E in the enzyme-deficient cells results from oxidant damage acting on a mildly unstable Hb variant. These observations may have important implications for the better understanding of the pathophysiology of Hb E/beta-thalassemia, globally the commonest important form of thalassemia.- - - - - - - - - - ranking = 0.4keywords = thalassemia (Clic here for more details about this article) |