1/61. The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma -thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family.The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma -thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma -thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma -thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma -thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma -thalassemia is responsible for neonatal hemolytic anemia in this family.- - - - - - - - - - ranking = 1keywords = hemolytic (Clic here for more details about this article) |
2/61. The beta-globin genotype E121Q/W15X (cd121GAA-->CAA/cd15TGG-->TGA) underlines Hb d/beta-(0) thalassaemia marked by domination of haemoglobin D.Among 13,525 haemoglobin analyses performed in our laboratory we detected 21 cases of haemoglobin D (Hb D) disease. Investigation of a family affected with this abnormal haemoglobin revealed two cases of Hb D/beta-(0) thalassaemia for the first time among Saudi arabs. The two patients were diagnosed as having chronic haemolytic anaemia of moderate severity on the basis of the haemoglobin level, haematocrit, mean corpuscular haemoglobin, mean corpuscular volume, reticulocyte count, red blood cell count microscopy, elevated serum conjugated and non-conjugated bilirubin, increased serum lactic dehydrogenase, and the occasional need for blood transfusions. Genetic analysis enabled the detection of compound heterozygosity for the missense E121Q (codon 121 GAA-->CAA) and stop W15X (codon 15 TGG-->TGA) mutations as causative of the clinical phenotype of Hb D-LosAngeles (Punjab)/beta-(0) thalassaemia. The disease manifested as domination of Hb D and moderate haemolytic anaemia. The co-inheritance of beta-(0) thalassaemia seems to be responsible for conferring the deleterious effect on the presentation of Hb D disease in these patients. The present result emphasizes the significance of molecular testing in resolving certain diagnostic ambiguities in haematology as in cases of heterozygous Hb D in association with beta-(0) thalassaemia which, by haemoglobin electrophoresis, may be misdiagnosed as Hb D homozygosity.- - - - - - - - - - ranking = 0.50434383731517keywords = anaemia (Clic here for more details about this article) |
3/61. Extramedullary haemopoiesis in thalassaemia intermedia: an unusual case of relapsing paraparesis in pregnancy.We report a case of thalassaemia intermedia complicated during two consecutive pregnancies by two episodes of spastic paraparesis due to compression of the spinal cord by extramedullary paravertebral masses. The patient was successfully treated by hypertransfusion and local irradiation. Compression of vital organs by the extramedullary masses must always be considered in chronic haemolytic anaemias during periods of increased haemopoietic demands like pregnancy. As relapses can not be excluded, a closer follow-up is needed. A dose of irradiation preventing from recurrences in the same anatomical area, seems necessary.- - - - - - - - - - ranking = 0.25217191865758keywords = anaemia (Clic here for more details about this article) |
4/61. Beta-thalassaemia of clinical significance in adult Jamaican Negroes.Over a 9-year period, three adult Negro patients with beta-thalassaemia of clinical significance were recognized out of approximately 185 000 new adult patients attending the University Hospital. These patients, aged 15-58 years, have clinical and haematological characteristics within the spectrum of beta-thalassaemia intermedia; which in this paper refers to phenotypes resulting from defects in beta-chain synthesis clinically intermediate between classical Cooley's anaemia and beta-thalassaemia trait, genetic classification being dependent on family study. family studies established the presence of two beta-thalassaemia genes conclusively in one case (proposita, family A); presumptively in another (propositus, family C); while in the remaining subject (proposita, family B), who has two similarly affected siblings, homozygosity is suspected, but not proven by family study. In simultaneous 59Fe and 51 Cr studies, estimates of effective erythropoiesis are in reasonable agreement with measurements of red cell destruction.- - - - - - - - - - ranking = 0.25217191865758keywords = anaemia (Clic here for more details about this article) |
5/61. 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 = 0.2keywords = hemolytic (Clic here for more details about this article) |
6/61. An individual with Hb-Lepore-baltimore- delta beta-thalassaemia in a Yugoslavian family.The clinical, haematological and biochemical findings in a person with delta beta-thalassaemia and Hb-Lepore are described. The patient was a 24-year-old student who suffered from anaemia of intermediate severity with late onset of the clinical manifestations, had minor bone and facial deformities, but had no necessity for regular transfusions. Haemoglobins A and A2 were absent in this individual, and the Hb-Lepore has been identified as Lepore-baltimore. Heterogeneity of gamma chain of the Hb-F follows the expected pattern. The study provides further evidence that neither beta nor delta chains are synthesized in cis to delta beta-thalassaemia or Hb-Lepore.- - - - - - - - - - ranking = 0.25217191865758keywords = anaemia (Clic here for more details about this article) |
7/61. Sickle cell syndromes. I. Hemoglobin SC-alpha-thalassemia.Hematologic and globin synthesis studies were performed in a black American family in which the genes for alpha-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait alpha-thalassemia; mother, HbC trait alpha-thalassemia, propositus, HbSC alpha-thalassemia; older sibling, alpha-thalassemia trait; and younger sibling, hemoglobin h disease. The child with HbSC-alpha-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2, 3-diphosphoglycerate (2, 3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin h disease exhibited 26% Bart's (gamma4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin h disease appeared, with HbH making up 6.5% of the total hemoglobin.- - - - - - - - - - ranking = 0.2keywords = hemolytic (Clic here for more details about this article) |
8/61. 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 = 0.2keywords = hemolytic (Clic here for more details about this article) |
9/61. Rare thalassemic syndrome caused by interaction of Hb Questembert (alpha1 codon 131, TCT>CCT, Ser>Pro) with an alpha-thalassemia-2 deletion: implications for diagnosis and management.Abnormal globin chain biosynthesis may result in deficient quantity (thalassemia) or structural variation (abnormal hemoglobins) and traditionally, they represent two phenotypically distinct groups of disorders. However, the phenotypic expression of unstable hemoglobin variants often combine features of thalassemia together with variable peripheral hemolysis. To achieve definitive diagnosis in a child presenting with hemolytic anemia along with features associated with thalassemia intermedia, we evaluated clinical, hematological, biochemical, globin biosynthetic and molecular data. Definitive diagnosis was achieved by dna analysis which characterized the proband to be a compound heterozygote for a common alpha-thalassemia-2 deletion (3.7 kb) and Hb Questembert (alpha131[H14] Ser>Pro) caused by a C>T mutation in codon 131 of the alpha1 globin gene in trans. The phenotype of thalassemia intermedia with marked dyserythropoiesis, found in patients inheriting alpha-thalassemia mutations along with unstable alpha-globin variants (i.e., alpha-thalassemic hemoglobinopathies), represents a distinct type of thalassemic syndrome. The proband in this study additionally had variable peripheral hemolysis, presumably related to characteristics of the unstable Hb Questembert. There is minimal experience for the management of such atypical cases and this case illustrates that it is probably insufficient to monitor clinical status in patients with such hemoglobinopathies based only on the levels of hemoglobin.- - - - - - - - - - ranking = 0.2keywords = hemolytic (Clic here for more details about this article) |
10/61. 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 = 0.4keywords = hemolytic (Clic here for more details about this article) |
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