scholarly journals X-linked syndrome of platelet dysfunction, thrombocytopenia, and imbalanced globin chain synthesis with hemolysis

Blood ◽  
1977 ◽  
Vol 50 (2) ◽  
pp. 303-316 ◽  
Author(s):  
AR Thompson ◽  
WG Wood ◽  
G Stamatoyannopoulos
Keyword(s):  
Family Members ◽  
Clinical Signs ◽  
Bleeding Disorder ◽  
Beta Thalassemia ◽  
Bleeding Tendency ◽  
Globin Chain ◽  
Platelet Dysfunction ◽  
Thalassemia Minor ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

An unusual family is described with a congenital bleeding disorder present in four males belonging to three generations. Of the three surviving affected males, all had splenomegaly and petechiae. The three had moderate thrombocytopenia (55–90 X 10(9)/liter) and markedly prolonged Ivy-template bleeding times (greater than 30 min). They were also noted to have reticulocytosis and, upon further investigation, imbalanced globin chain synthesis resembling that of beta-thalassemia minor. Studies on nine additional family members in four generations were normal except for slight elevations of reticulocyte counts in female members, one of whom had the abnormal globin chain synthesis ratio. In male members, the bleeding tendency and clinical signs always occurred in the presence of the globin chain synthesis defect and reticulocytosis. This previously undescribed condition was apparently transmitted as an X-linked disorder.

scholarly journals X-linked syndrome of platelet dysfunction, thrombocytopenia, and imbalanced globin chain synthesis with hemolysis

Blood ◽  
1977 ◽  
Vol 50 (2) ◽  
pp. 303-316 ◽  
Author(s):  
AR Thompson ◽  
WG Wood ◽  
G Stamatoyannopoulos
Keyword(s):  
Family Members ◽  
Clinical Signs ◽  
Bleeding Disorder ◽  
Beta Thalassemia ◽  
Bleeding Tendency ◽  
Globin Chain ◽  
Platelet Dysfunction ◽  
Thalassemia Minor ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract An unusual family is described with a congenital bleeding disorder present in four males belonging to three generations. Of the three surviving affected males, all had splenomegaly and petechiae. The three had moderate thrombocytopenia (55–90 X 10(9)/liter) and markedly prolonged Ivy-template bleeding times (greater than 30 min). They were also noted to have reticulocytosis and, upon further investigation, imbalanced globin chain synthesis resembling that of beta-thalassemia minor. Studies on nine additional family members in four generations were normal except for slight elevations of reticulocyte counts in female members, one of whom had the abnormal globin chain synthesis ratio. In male members, the bleeding tendency and clinical signs always occurred in the presence of the globin chain synthesis defect and reticulocytosis. This previously undescribed condition was apparently transmitted as an X-linked disorder.

scholarly journals Globin Chain Synthesis in the Marrow and Reticulocytes of Beta Thalassemia, Hemoglobin H Disease, and Beta Delta Thalassemia

Blood ◽  
1972 ◽  
Vol 40 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Mordechai Shchory ◽  
Bracha Ramot
Keyword(s):  
Bone Marrow ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Thalassemia Intermedia ◽  
Thalassemia Minor ◽  
Order Of Magnitude ◽  
Hb H Disease ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract α, β, and γ globin chain synthesis in bone marrow and peripheral blood reticulocytes were studied in two patients with thalassemia major, two with thalassemia intermedia, one with thalassemia minor, one with Hb H disease, and one with homozygous βδ-thalassemia. Nine nonthalassemic patients served as controls. In thalassemia major, a marked imbalance of α- to β-chain synthesis was found in the bone marrow as well as in reticulocytes. The imbalance, however, was slightly more evident in the latter. In the patients with thalassemia intermedia and minor the α- to β-globin chain ratios in the reticulocytes were of the same order of magnitude, despite the marked clinical differences between thalassemia intermedia and minor. A balanced synthesis was found in the bone marrow of the patient with thalassemia minor. The bone marrow globin synthesis in thalassemia intermedia was not studied. Contrary to that in Hb H disease and βδ-thalassemia, the imbalance was more apparent in the bone marrow. In the latter, no evidence for imbalance was detected in the reticulocytes. These results point out the need for further studies on globin chain synthesis in the bone marrow and reticulocytes of patients With the various thalassemia syndromes and the effect of the free globin chain pool on those results.

scholarly journals Delta +-thalassemia in Sardinia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 341-345 ◽  
Author(s):  
M Pirastu ◽  
R Galanello ◽  
MA Melis ◽  
C Brancati ◽  
A Tagarelli ◽  
...  
Keyword(s):  
Restriction Endonuclease ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Globin Chain ◽  
New Type ◽  
Polymorphic Restriction ◽  
Chain Synthesis ◽  
Double Heterozygosity ◽  
Globin Chain Synthesis

Abstract We have defined a new type of delta-thalassemia in which beta-globin chain synthesis is incompletely suppressed. Homozygotes have unusually low HbA2 levels, and double heterozygosity for this delta-thalassemia gene and beta-thalassemia normalizes the HbA2 level. The delta- thalassemia occurs on a chromosome that is identifiable using polymorphic restriction endonuclease sites. We call this condition delta +-thalassemia, to distinguish it from the previously described delta 0-thalassemia syndromes in which no delta-globin chain synthesis occurs.

scholarly journals A family with segregating triplicated alpha globin loci and beta thalassemia

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1035-1040 ◽  
Author(s):  
R Galanello ◽  
R Ruggeri ◽  
E Paglietti ◽  
M Addis ◽  
MA Melis ◽  
...  
Keyword(s):  
Globin Gene ◽  
Phenotypic Expression ◽  
Beta Thalassemia ◽  
Heterozygous State ◽  
Globin Chain ◽  
Homozygous State ◽  
Alpha Globin ◽  
Triple Alpha ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract In this article we report a Sardinian family, in which a beta- thalassemia gene and a triple alpha-globin loci, counterpart of the rightward deletion type alpha-thalassemia-2, were segregating. The analysis of the genotype-phenotype correlations in the different family members allowed us to give an outline of the manifestations associated with different genotype combinations. The heterozygote for the triple alpha-loci showed no consistent abnormal clinical or hematologic characteristics and presented balanced alpha/beta-globin chain synthesis. In the homozygous state for this lesion, the only phenotypic expression was a slightly imbalanced globin chain synthesis. The combination of heterozygous beta-thalassemia with the heterozygous state for the triple alpha-globin loci produced no clinical manifestations and showed a hematologic phenotype indistinguishable from that of heterozygous beta-thalassemia. On the other hand, the combination of the homozygous state for the triple alpha-globin gene loci and the heterozygous state for beta-thalassemia produced a clinical picture of thalassemia intermedia with a very mild clinical course, minor increase of fetal hemoglobin (HbF) levels, and a pronounced imbalance of globin chain synthesis.

scholarly journals Globin chain synthesis in HbD (Punjab)-beta-thalassemia

Blood ◽  
1976 ◽  
Vol 47 (1) ◽  
pp. 113-120 ◽  
Author(s):  
RF Rieder
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Globin Chains ◽  
Mild Anemia ◽  
Thalassemia Trait ◽  
Chain Synthesis ◽  
Hbd Punjab ◽  
Globin Chain Synthesis

Abstract A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta- thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.

RECONSTRUCTION OF THE THUMB WITH A MODIFIED WRAP-AROUND FLAP IN A PATIENT SUFFERING FROM β-THALASSEMIA MINOR

Hand Surgery ◽  
2011 ◽  
Vol 16 (03) ◽  
pp. 361-365
Author(s):  
M. Galeano ◽  
G. Checcucci ◽  
M. Ceruso
Keyword(s):  
Globin Chain ◽  
Thumb Reconstruction ◽  
First Case ◽  
Thalassemia Minor ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Thalassemia is a congenital hemolytic disorder caused by a partial or complete deficiency of α- or β-globin chain synthesis. It has been seen that thalassemic patients exhibit an increased frequency of thrombotic events. The article presents the first case of thumb reconstruction with a modified wrap-around flap in a patient suffering from β-thalassemia minor.

scholarly journals A family with segregating triplicated alpha globin loci and beta thalassemia

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1035-1040
Author(s):  
R Galanello ◽  
R Ruggeri ◽  
E Paglietti ◽  
M Addis ◽  
MA Melis ◽  
...  
Keyword(s):  
Globin Gene ◽  
Phenotypic Expression ◽  
Beta Thalassemia ◽  
Heterozygous State ◽  
Globin Chain ◽  
Homozygous State ◽  
Alpha Globin ◽  
Triple Alpha ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

In this article we report a Sardinian family, in which a beta- thalassemia gene and a triple alpha-globin loci, counterpart of the rightward deletion type alpha-thalassemia-2, were segregating. The analysis of the genotype-phenotype correlations in the different family members allowed us to give an outline of the manifestations associated with different genotype combinations. The heterozygote for the triple alpha-loci showed no consistent abnormal clinical or hematologic characteristics and presented balanced alpha/beta-globin chain synthesis. In the homozygous state for this lesion, the only phenotypic expression was a slightly imbalanced globin chain synthesis. The combination of heterozygous beta-thalassemia with the heterozygous state for the triple alpha-globin loci produced no clinical manifestations and showed a hematologic phenotype indistinguishable from that of heterozygous beta-thalassemia. On the other hand, the combination of the homozygous state for the triple alpha-globin gene loci and the heterozygous state for beta-thalassemia produced a clinical picture of thalassemia intermedia with a very mild clinical course, minor increase of fetal hemoglobin (HbF) levels, and a pronounced imbalance of globin chain synthesis.

scholarly journals Retrovirus-mediated transfer of the erythropoietin gene in hematopoietic cells improves the erythrocyte phenotype in murine beta- thalassemia

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 928-933 ◽  
Author(s):  
JL Villeval ◽  
P Rouyer-Fessard ◽  
N Blumenfeld ◽  
A Henri ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Bone Marrow Cells ◽  
Elevated Serum ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Alpha Globin ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract Repeated injections of large doses of erythropoietin (Epo) have been shown to be of benefit in the treatment of murine and human beta- thalassemia. To determine whether Epo gene therapy could replace this treatment for long-term periods, lethally irradiated beta-thalassemic (Hbbd3th haplotype) and normal DBA/2J (Hbbd haplotype) mice were grafted with syngeneic bone marrow cells infected with a retroviral vector carrying the Epo cDNA. In normal mice, dysregulated Epo production induced elevated serum Epo levels (176 +/- 68 mU/mL), high hematocrit levels (73% +/- 8%), and elevated beta-minor globin chain synthesis. In contrast, in thalassemic mice, moderate increases in the hematocrit levels (from 33% +/- 1% to 43% +/- 9%), associated with limited increases in the initially elevated Epo levels (from 83 +/- 22 to 190 +/- 230 mU/mL), were recorded 2 months after transplantation. In mice in which the hematocrit increased most, from 33% +/- 1% before transplantation to 49% +/- 10%, the retroviral Epo gene expression induced a striking improvement of the beta-thalassemic syndrome. These mice exhibited normal or near-normal beta/alpha-globin chain synthesis ratios, induced by the activation of the beta-minor chain. This led to the elimination of the high amounts of unpaired alpha chains in erythrocytes and finally reduced the reticulocyte count despite the permanent Epo stimulation. These results show that efficient Epo gene expression corrects the erythrocyte phenotype of the mouse beta- thalassemic syndrome. However, the incidence of lethal polycythemia or of transient improvements indicates that the present strategy is only the first step toward such indirect gene therapy.

scholarly journals Globin chain synthesis in HbD (Punjab)-beta-thalassemia

Blood ◽  
1976 ◽  
Vol 47 (1) ◽  
pp. 113-120
Author(s):  
RF Rieder
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Globin Chains ◽  
Mild Anemia ◽  
Thalassemia Trait ◽  
Chain Synthesis ◽  
Hbd Punjab ◽  
Globin Chain Synthesis

A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta- thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.

scholarly journals Retrovirus-mediated transfer of the erythropoietin gene in hematopoietic cells improves the erythrocyte phenotype in murine beta- thalassemia

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 928-933 ◽  
Author(s):  
JL Villeval ◽  
P Rouyer-Fessard ◽  
N Blumenfeld ◽  
A Henri ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Bone Marrow Cells ◽  
Elevated Serum ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Alpha Globin ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Repeated injections of large doses of erythropoietin (Epo) have been shown to be of benefit in the treatment of murine and human beta- thalassemia. To determine whether Epo gene therapy could replace this treatment for long-term periods, lethally irradiated beta-thalassemic (Hbbd3th haplotype) and normal DBA/2J (Hbbd haplotype) mice were grafted with syngeneic bone marrow cells infected with a retroviral vector carrying the Epo cDNA. In normal mice, dysregulated Epo production induced elevated serum Epo levels (176 +/- 68 mU/mL), high hematocrit levels (73% +/- 8%), and elevated beta-minor globin chain synthesis. In contrast, in thalassemic mice, moderate increases in the hematocrit levels (from 33% +/- 1% to 43% +/- 9%), associated with limited increases in the initially elevated Epo levels (from 83 +/- 22 to 190 +/- 230 mU/mL), were recorded 2 months after transplantation. In mice in which the hematocrit increased most, from 33% +/- 1% before transplantation to 49% +/- 10%, the retroviral Epo gene expression induced a striking improvement of the beta-thalassemic syndrome. These mice exhibited normal or near-normal beta/alpha-globin chain synthesis ratios, induced by the activation of the beta-minor chain. This led to the elimination of the high amounts of unpaired alpha chains in erythrocytes and finally reduced the reticulocyte count despite the permanent Epo stimulation. These results show that efficient Epo gene expression corrects the erythrocyte phenotype of the mouse beta- thalassemic syndrome. However, the incidence of lethal polycythemia or of transient improvements indicates that the present strategy is only the first step toward such indirect gene therapy.

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