Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THALASSEMIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed2004

Short stature in beta-thalassemia minor subjects.

BACKGROUND: Numerous disturbances in growth and development have been observed and demonstrated in homozygote beta-thalassemia patients. However, short stature in thalassemia minor subjects, who have a minor defect in hemoglobin chain synthesis, has not yet been studied. MATERIAL/METHODS: In this cross-sectional study, the heights of 100 thalassemia minor subjects in the age group of 2-18 years and their parents were measured and analyzed. If the subject were in the 3-10 percentile range of height based on standardized sex and age curves, several follow-ups with complete history and physical examinations for a period of one year were preformed. If the healthy carrier's height was below the 3rd percentile, history, physical examination, and paraclinical examinations, including BUN, creatinine, electrolytes, serum alkaline phosphatase, thyroid function tests, growth hormone and cortisol levels, arterial blood gas, radiography of the left hand and wrist, etc, were also checked. One hundred healthy children were randomly chosen as a control group and matched for demographic characteristics with our healthy carrier subjects. RESULTS: Mean +/- standard deviation for the age of our subjects was 6.62+/-3.63 years old. Twenty-seven (27%) of the patients had short stature. Except for hemoglobin (with a mean of 11.5 g/l), all other paraclinical data were normal. CONCLUSIONS: We concluded that short stature was significantly more prevalent in the healthy beta thalassemia minor subjects than in the control group (p<0.001). Therefore, thalassemia minor can cause short stature.

Adolescent↗
PubMed2005

Genetic modifiers of beta-thalassemia.

As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with apparently identical genotypes can have many different clinical conditions even in simple monogenic disorders. Beta thalassemia occurs when there is a deficiency in the synthesis of beta globin chains. The clinical manifestations of beta thalassemia are extremely diverse, spanning a broad spectrum from severe anemia and transfusion-dependency to the asymptomatic state of thalassemia trait. The remarkable phenotypic diversity of the beta thalassemias is prototypical of how a wide spectrum of disease severity can be generated in single gene disorders. The most reliable and predictive factor of disease phenotype is the nature of the mutation at the beta globin locus itself. However, relating phenotype to genotype is complicated by the complex interaction of the environment and other genetic factors at the secondary and tertiary levels, some implicated from family studies, and others, as yet unidentified. This article reviews the clinical and hematologic diversity encountered in beta thalassemia with an overview of the modifier genes that moderate their disease expression.

Alleles↗
PubMed2005

Enhanced maturation and proliferation of beta-thalassemia/Hb E erythroid precursor cells in culture.

Upon erythroid cell maturation in vivo, beta-thalassemic erythroid cells accumulate unmatched unstable alpha-globin chains that are believed to be a causal factor in such cell destruction. This study showed that beta-thalassemia/Hb E erythroid precursor cells from peripheral blood had accelerated maturation, and could mature to the terminal erythroid stage. During the early period of cell culture, erythroid precursor cells derived from subjects with the more severe form of beta-thalassemia/Hb E had higher rate of erythroid maturation. In addition, peripheral blood mononuclear cells from beta-thalassemia/Hb E subjects had higher erythroid proliferative potential than cells derived from normal controls. Erythroid proportion in the more severe beta-thalassemia/Hb E cases was less than that of the milder cases. Premature apoptosis was not observed during the 15 days of erythroid cell culture from both beta-thalassemia/Hb E and normal subjects.

Adolescent↗
PubMed2006

[Phenotyping and genotyping studies in a family with the compound heterozygosity deltabeta Thalassemia/beta(IVSII-849) Thalassemia].

The propositus is a two year old child with a severe hemolytic anemia and increased level of Hb F. The Hbs A, A2 and F were eluted and quantitated by cation exchange high-performance liquid chromatography (HPLC-CE). DNA was isolated from peripheral blood leukocytes by a salting-out extraction procedure. The beta globin gone was amplified and the presence of the beta thalassemia mutation was determined by PCR followed of Reverse Dot Blot. Her hematological parameters were as follows: Hb: 7.0 g/dL, Hct: 24.8%, VCM: 87.4 fl, CHCM: 27.8 fl. The haemoglobin study showed an 97% increase of Hb F and Hb A2 normal. The molecular study suggested the presence of beta(IVSII-829) mutation in trans to deltabeta Thalassemia. The propositus inherited her mother's deltabeta-thalassemia gene mutation and her father's beta(IVSH-829) mutation. This is the first time the diagnosis has been performed in a Venezuelan family at-risk of compound heterozygotes for beta-thalassemia and delta beta-thalassemia.

Black People↗
PubMed2006

Molecular characterization of thalassemia intermedia in Indians.

Thalassemia intermedia shows considerable heterogeneity. The purpose of this study was to evaluate the prevalence and effect of common molecular determinants in thalassemia intermedia. In 73 cases of thalassemia intermedia, the possible molecular basis was co-existent a-deletions (n=16/50), homozygous XmnI polymorphism (n=17/50), both factors (n=3/50), and milder beta-alleles (n=9/50) in homozygous beta-thalassemia (total 50 cases). In heterozygous beta-thalassemia, alphaalphaalphaanti-3.7 triplication was the predominant factor (14/23 cases).

Gene Deletion↗
PubMed2006

Epidemiology of hepatitis B, hepatitis C, and human immunodeficiency virus infecions in patients with beta-thalassemia in Iran: a multicenter study.

BACKGROUND: Though regular blood transfusion improves the overall survival of patients with beta-thalassemia, it carries a definite risk of infection with blood-borne viruses. We carried out this multicenter study to provide epidemiologic data on hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection among Iranian beta-thalassemic patients. Moreover, HCV infection-associated risk factors were investigated in this population. METHODS: Seven hundred and thirty-two patients with beta-thalassemia major or beta-thalassemia intermedia, selected from five provinces of Iran including Tehran (n = 410), Kerman (n = 100), Qazvin (n = 95), Semnan (n = 81), and Zanjan (n = 46), were enrolled in this study. Using ELISA, their sera were tested for HBsAg, HBcAb, HBsAb, HCVAb, and HIVAb. The positive HCVAb results were confirmed by RIBA-2nd generation. RESULTS: The study sample consisted of 413 males and 319 females, with a mean +/- SD age of 17.9 +/- 9.0 years. One hundred forty-one (19.3%) patients were HCVAb positive; 11 (1.5%) were HBsAg positive. No one was HIVAb positive. Univariate analysis showed that beta-thalassemia major (P = 0.01), older age (P = 0.001), longer transfusion duration (P = 0.000), HBsAg seropositivity (P = 0.03), and higher serum ferritin level (P = 0.002) were significantly associated with a higher prevalence of HCV. Furthermore, the prevalence of HCV infection dropped significantly after the implementation of blood donors screening (22.8% vs. 2.6%; P = 0.000). Using multivariate analysis, beta-thalassemia major (P = 0.002), age (P < 0.001), serum ferritin level (P < 0.001), as well as consumption of unscreened blood (P = 0.003), were independent factors associated with HCV infection. CONCLUSION: The prevalence of HCV infection is much higher among Iranian beta-thalassemic patients as compared with HBV and HIV infections. Routine screening of donated blood for HCV is highly recommended.

Adolescent↗
PubMed2006

Prevalence of growth and puberty failure with respect to growth hormone and gonadotropins secretion in beta-thalassemia major.

BACKGROUND: Present transfusion protocols have increased the life expectancy of patients with beta-thalassemia major, but siderosis is a major clinical complication of the treatment. Short stature and hypogonadism are extremely frequent in patients with thalassemia. To investigate the influence of age at the onset of blood transfusion, iron chelation therapy, and serum ferritin levels on growth and pubertal development in thalassemic patients, and the prevalence of these endocrine complications with respect to pituitary somatotropic and gonadotropic functions, this study was designed. METHODS: Clinical data of 158 patients (82 females and 76 males) with thalassemia major, aged 10 - 20 years (mean age: 15.1 +/- 4.8 years) were collected from a pediatric hematology clinic in Tehran. Height was measured and stages of puberty were determined by a pediatric endocrinologist. Serum ferritin concentration, liver function tests, serum calcium and phosphorus, blood sugar, free thyroxine (FT4), TSH, FSH, LH, dehydroepiandrosterone sulfate, testosterone (in boys), estradiol (in girls), and insulin-like growth factor I were measured after overnight fasting. In patients with a height more than 2 standard deviation below the mean, the growth hormone stimulation test was considered. Bone age was determined in all patients. RESULTS: Thalassemic patients in this study showed a high prevalence of short stature (62%) and hypogonadism (69%). We found a low serum level of gonadotropins (FSH and LH) in over 14-year-old patients with impaired puberty, which indicated that hypogonadotropic hypogonadism is responsible for this complication. Results of growth hormone provocative tests and serum insulin-like growth factor I levels in short stature patients showed a reduced growth hormone response in 38% and low insulin-like growth factor I levels in 42% of thalassemic patients. Short stature and hypogonadism were more common in patients with serum ferritin levels above 2000 microg/L and these complications were significantly more frequent in patients who started treatment later than that of the patients who started treatment in the first years of life (P < 0.001). CONCLUSION: Short stature and hypogonadism are extremely frequent in our patients with thalassemia, but correct blood transfusion and appropriate iron chelation therapy can prevent or limit these complications. These data support the need for vigilant follow-up of patients with thalassemia in order to treat endocrine dysfunction at an appropriate age.

Adolescent↗
PubMed2006

Risk of a couple having a child with severe thalassemia syndrome, prevalence in lower northern Thailand.

Thalassemia screening in pregnant women and their spouses was performed at Buddhachinaraj Provincial Hospital and 8 community hospitals in Phitsanulok; lower northern Thailand. The prevalence of thalassemic carrier state was determined of 1,198 couples. Of these, 4.8% had heterozygous alpha thalassemia-1, 1.6% had heterozygous beta thalassemia, 12.4% had heterozygous hemoglobin (Hb) E, 2.7% had homozygous Hb E and 0.25% of others had abnormal Hb. Eighteen at risk couples (1.5%) were identified. Fifteen couples were at risk for compound heterozygous Hb E / beta thalassemia and the remaining 3 were at risk for homozygous alpha thalassemia-1. Prenatal diagnosis (cordocentesis) was performed in 4 couples at risk, but no fetuses with severe thalassemic disease were detected.

Adult↗
PubMed1992

Automated measurement of red blood cell microcytosis and hypochromia in iron deficiency and beta-thalassemia trait.

Some routine red blood cell (RBC) measurements and indexes (count, mean volume, volume dispersion, and mean hemoglobin [HGB] concentration) can be used to differentiate iron deficiency from heterozygous beta-thalassemia. A number of formulas that incorporate two or more of these measurements have been described to amplify such differences. The H*1 hematology analyzer directly measures volume and HGB concentration of individual RBCs. We have assessed the diagnostic usefulness of conventional and new RBC measurements provided by the H*1 on a learning data set that comprised 119 patients with iron deficiency and 172 patients with beta-thalassemia trait, both untreated and uncomplicated. The most striking finding was the inverse behavior of percentages of microcytes (volume, less than 60 fL) and hypochromic RBCs (HGB concentration, less than 280 g/L) in the two conditions. In 162 of 172 patients with beta-thalassemia trait, the percentage of microcytes (mean, 33.1%; central 95th percentile range, 9.2% to 54.5%) was higher than the percentage of hypochromic RBCs (mean, 13.9%; central 95th percentile range, 1.7% to 24.7%). In 105 of 119 patients with iron deficiency, on the contrary, the percentage of hypochromic cells (mean, 34.6%; central 95th percentile range, 9.7% to 73.1%) was higher than the percentage of microcytes (mean, 12.8%; central 95th percentile range, 1.7% to 29.6%). The ratio between the percentage of microcytes and the percentage of hypochromic cells provided by the H*1 (microcytic-hypochromic ratio) was useful in differentiating the two types of microcytic anemia: with the use of a discriminant value of 0.9, the discriminant efficiency of the microcytic-hypochromic ratio was 92.4% (95% confidence interval, 88.8% to 95.2%), higher than that of the five previously described discriminant formulas and simple RBC measurements. When assessed on a test data set that comprised 149 unselected cases of microcytic anemia, a microcytic-hypochromic ratio lower than 0.9 demonstrated high sensitivity (94.0%), specificity (92.3%), and predictive value (94.0%) for the presence of iron-deficient erythropoiesis in patients with isolated iron deficiency, polycythemia vera treated by phlebotomy, and iron deficiency complicating heterozygous thalassemia. In conclusion, our results showed that iron-deficient erythropoiesis is characterized by the production of RBCs with a severely decreased HGB concentration, while microcytes of beta-thalassemia trait are generally smaller, with a more preserved HGB concentration. Such properties, as assessed by the H*1 hematology analyzer, are very useful in distinguishing these two common types of microcytic anemia.

Anemia, Hypochromic↗
PubMed1977

[Clinical and biological aspects of beta-thalassemia. Apropos of 176 cases].

The study of 176 subjects with beta-thalassemia, associated or not with a hemoglobinopathy, shows great diversity. The hemoglobin C thalassemias are less severe and form a fairly homogeneous group. Sickle cell thalassemia cases have more marked anemia and the disease takes on more varied forms, no doubt because the main mechanism of the anemia, the hyperhemolysis, is influenced by several factors which have a variable effect on the clinical picture. Unassociated thalassemias seem the most polymorphic. Although it seems that in certain foci the beta-thalassemias are fairly stereotyped, this first study shows in Algeria great heterogeneity. All forms are observed both clinically and in the laboratory. Present classifications have not supplied a sufficiently operative model. It is not doubt necessary to await further progress in the laboratory to classify these diseases more precisely.

Adolescent↗
PubMedDate not supplied

[The relationship of clinical severity and roentgenologic findings in beta thalassemia].

There were altogether 68 patients suffered from beta-thalassemia in the Veterans General Hospital from 1979 to 1986. However only 18 patients had abnormal roentgenologic findings. They were 7 males and 11 females. Their ages ranged from 8 months to 47 years with an average of 13 years. Clinically beta-thalassemia was divided into 3 types: 1) thalassemia major, 2) thalassemia intermediate, 3) thalassemia minor. The osteoporosis, hepatosplenomegaly, and extramedullary hematopoiesis with pseudo-tumor formation. We concluded that the roentgenologic manifestation of the patient was more in patients with major or intermediate type.

Adolescent↗
PubMedDate not supplied

Fetal hemoglobin heterogeneity in Brazilian newborns and beta-thalassemia homozygotes.

The gamma chain composition of HbF in 37 beta-thalassemia homozygotes and 85 unselected newborn babies from Brazil was studied by high performance liquid chromatography (HPLC). The G gamma value of 59.5 +/- 7.5% (mean +/- SD) obtained for the beta-thalassemia homozygotes was significantly lower than the newborn value of 71.2 +/- 4.2%. The A gamma T gene frequency was 0.159 for the newborns and 0.454 for the thalassemia homozygotes. The A gamma T gene occurred both in chromosomes bearing the beta(0)-thalassemia gene and those with the beta(+)-thalassemia gene.

Brazil↗
PubMed1989

Incidence study of heterozygous beta-thalassemia in northern Taiwan.

Determined with automated cell counters, mean corpuscular volume (MCV) of erythrocytes was screened in 4,100 consecutive gravidas who delivered at the National Taiwan University Hospital during the period from July 1986 through August 1988. In total, 248 (6%) women had MCV less than 80 fl and were recruited for further study, including Hb A2 quantitation using microcolumn chromatography, cord blood Hb electrophoresis on cellulose acetate membrane, and alpha-globin gene mapping in some cases. In the first control group of 51 cases of obligate carriers of heterozygous beta-thalassemia, the mean MCV +/- standard deviation (SD) was 67 +/- 4.5fl (range 59 to 76fl) and the mean Hb A2 +/- SD was 6.53 +/- 1.31% (range 4.3 to 8.0%). In the second control group of 40 cases of obligate carriers of heterozygous alpha-thalassemia 1, the mean MCV +/- SD was 70 +/- 3.7fl (range 63 to 78fl) and the mean Hb A2 +/- SD was 2.28 +/- 0.54% (range 1.5 to 3.8). Forty-five microcytic women (1.1%) had Hb A2 over 4%, a cut-off level for heterozygous beta-thalassemia in our laboratory. In this study group, the mean MCV +/- SD was 68 +/- 5.4 and the mean Hb A2 +/- SD was 6.03 +/- 1.41. None of the newborns delivered by these women had Hb Bart's in cord blood. alpha-Globin gene mapping using DNA hybridization was done in 14 women, and the results were all compatible with the exclusion of deletional alpha-thalassemia. It is concluded that approximately 1% of people in northern Taiwan are beta-thalassemia heterozygotes.

Erythrocyte Indices↗
PubMed1987

The beta-globin gene on the Chinese delta beta-thalassemia chromosome carries a promoter mutation.

A new type of delta beta-thalassemia characterized by decreased expression of the beta-globin gene and increased expression of both G gamma and A gamma globin gene in the absence of a detectable deletion has recently been described in the Chinese population. In this study we characterize the mutant beta-globin gene from this delta beta-thalassemia chromosome. An A to G transversion is identified in the "ATA" sequence of the promoter region that leads to decreased expression of the beta-globin gene in vivo and in vitro. We also demonstrate the presence of this mutation in every individual with a high fetal hemoglobin phenotype in this family and its absence in every individual with a normal hemoglobin phenotype. This same promoter mutation has recently been detected in Chinese beta-thalassemia genes where it is present on chromosomes of the same haplotype as that of the delta beta-thalassemia chromosome we are studying. These data support the hypothesis that an as yet unidentified mutation occurred on the ancestral chromosome carrying the promoter mutation and subsequently gave rise to the delta beta-thalassemia phenotype.

China↗
PubMed1987

DNA sequence analysis of the Dutch beta zero-thalassemia deletion.

The Dutch beta zero-thalassemia has relatively few clinical symptoms in the homozygote. Heterozygotes have levels of fetal hemoglobin (4-11%) comparable to delta beta-thalassemia, and much higher than in typical beta zero-thalassemia. To analyze this deletion, we have cloned the abnormal 10 kb Bgl II fragment that contains the delta-globin gene into phage lambda vector EMBL4. A Hind III-Xba I fragment that includes the endpoints of the deletion was subcloned into plasmid pUC 19 and partially sequenced by the dideoxy method. The sequence of the Dutch beta zero-thalassemia DNA is like that of normal 5' DNA to 8920 (the numbering system is from reference 2). The sequence from 8915-8920 is AAATTT, which is also the normal 3' sequence from 21537-21542. From this point on, the Dutch beta zero-thalassemia sequence is like that of the normal 3' DNA. The deletion is therefore 12.6 kilobases, rather than 10 as originally estimated. It is similar to several other beta-globin gene deletions in terminating in a region of Kpn I repeated sequences, and having several base pairs of homology between 5' and 3' sequences at the break points.

Base Sequence↗
PubMed1987

Erythrocyte membrane skeleton abnormalities in severe beta-thalassemia.

The protein composition of ghosts, inside-out vesicles (IOV), and membrane skeletons (MS) of erythrocytes (RBC) from splenectomized (spx) and nonsplenectomized (non-spx) patients with beta-thalassemia major and beta-thalassemia intermedia was determined. Ghosts from spx thalassemia intermedia patients had a significant increase in their globin content (which was mostly heme reactive) and contained extra polypeptides in the protein 4.2 to 5 and 6-globin areas. The Triton-extracted MS from all of the thalassemic patients showed two major abnormalities: they retained up to twice the amount of protein 3 when compared with controls; they had a significant increase in their globin content, the concentration of which was independent of their protein 3 content. Analysis of the IOV revealed no differences between those prepared from normal controls and those of the patients. MS from spx thalassemia intermedia patients were grossly abnormal when examined by scanning electron microscopy and they exhibited aggregates of material that on transmission electron microscopy suggested the presence of globin precipitates. We propose that, although the integral protein composition, as reflected in the IOV, from severely affected beta-thalassemics is intact, their MS assembly is deranged. The altered skeletal structure of thalassemic RBC could result from attachment of denatured globin to the skeleton components. These abnormalities may contribute to the premature cell death seen in severe beta-thalassemia.

Cytosol↗
PubMed1987

Patient age distribution in thalassemia major: changes from 1973 to 1985.

Major advances have occurred in the treatment and prevention of thalassemia major, but their impact on incidence and survival have not been well assessed. In 1973, a survey was done of the ages of 243 living patients with thalassemia major followed at 12 centers in the United States and Canada. Twenty-two percent were younger than 5 years and 2.1% were older than 25 years of age (mean 11.4 +/- 6.7 [SD] years). In 1985, there were 303 patients at the same centers; 11% were younger than 5 years and 7.9% were older than 25 years (mean 14.2 +/- 7.3 years). A similar pattern was found in Connecticut, characterized by a marked decrease of new cases of thalassemia major during the past 15 years. This was not a result of fewer persons at genetic risk or a change in marital ethnic choices. Eleven of 14 families who had a child with thalassemia major assured that another affected child would not be born by having no more children, using prenatal diagnosis, or having therapeutic abortions. Extensive community programs of education and testing for thalassemia trait in Connecticut may also have contributed to the observed reduction in new cases.

Adolescent↗
PubMed1979

Hb P-Nilotic in association with beta0-thalassemia: cis-mutation of a hemoglobin betaA chain regulatory determinant?

Hb P-Nilotic which is produced by a hybrid of beta and delta genes was found in several members of a Sudanese family, three of whom had an associated beta-thalassemia. Chemical analyses confirmed the crossover between positions 22 and 50 of the beta delta P chain. The Hb p-Nilotic heterozygote had completely normal hematology, but the patients with the Hb P-Nilotic--beta-thalassemia condition had moderately severe clinical and hematological abnormalities which were considerably more pronounced than those in the father who had a beta-thalassemia heterozygosity. The absolute cellular contents of normal and abnormal non-alpha chains in these subjects and the results of in vitro chain synthesis analyses suggested that the thalassemia gene in this family is of the beta0 type and that the beta A gene which is present in cis to the beta delta P gene is incapable of being stimulated when the beta0-thalassemia determinant is present in trans. It is proposed that a number of recombination events produced a beta delta P hydrid gene with duplication of the beta A gene in cis as well as a change in an untranscribed strand of DNA which controls the expression of the beta A gene.

Bone Marrow↗