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 469 records · Page 26Linked to original sources
PubMed1982

The interaction of alpha-thalassemia and homozygous sickle-cell disease.

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (alpha-/alpha-), may be heterozygous for alpha-thalassemia 2 (alpha-/alpha alpha), or may have a normal alpha-globin-gene complement (alpha alpha/alpha alpha). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin A2, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled cell counts, and serum total bilirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (alpha-/alpha alpha) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in other two subgroups. These data confirm previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.

Adolescent↗
PubMed1988

Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion.

Diabetes mellitus in patients receiving hypertransfusion for thalassemia major is usually attributed to damage to beta cells. To determine whether iron overload leads to insulin resistance before the development of insulin deficiency, insulin was infused (by euglycemic insulin-clamp technique) into 12 children with thalassemia (4 of whom were prepubertal, and 8 pubertal) who had normal or only moderately impaired glucose tolerance and who were receiving chelation therapy. Although insulin-stimulated glucose metabolism in the prepubertal children with thalassemia was similar to that in controls (normal prepubertal children) (319 +/- 23 vs. 314 +/- 41 mg per square meter of body-surface area per minute, P not significant), the response to insulin was markedly impaired in the pubertal children with thalassemia (155 +/- 18 vs. 224 +/- 15 mg per square meter per minute in normal pubertal controls, P less than 0.01). Plasma insulin levels rose excessively after oral glucose administration in the pubertal subjects with thalassemia, but not in the prepubertal patients (P less than 0.001). Furthermore, in response to a standard hyperglycemic stimulus, insulin levels in the pubertal patients rose to two to three times greater than normal and C-peptide levels became significantly elevated. Our data suggest that insulin resistance and increased insulin secretion develop in older children with thalassemia treated with long-term hypertransfusion therapy before the development of diabetes.

Adolescent↗
PubMed1970

Cell-free hemoglobin synthesis in beta-thalassemia.

Human ribosomes obtained from the reticulocytes of patients having either homozygous beta-thalassemia (thalassemia ribosomes) or a hematological disorder unrelated to thalassemia ("normal" ribosomes) have been utilized in a cell-free system highly active in the synthesis of intact human globin chains. This system is dependent on the addition of a ribosomal wash fraction from reticulocytes that contains factors necessary for chain initiation. In response to the ribosomal wash fraction, isolated from either thalassemia, normal human, or rabbit reticulocytes, normal human ribosomes synthesize equal amounts of alpha and beta chains. In contrast, in response to all three types of ribosomal wash fractions, thalassemia ribosomes synthesize 8-times more alpha than beta chains, a ratio similar to that produced in the intact cells of these patients. The molecular defect in beta-thalassemia, therefore, does not appear to be associated with initiation factors.

Anemia, Hemolytic, Autoimmune↗
PubMed2006

Jaundice and alpha gene triplication in beta-thalassemia: association or causation?

There are few studies investigating alpha globin gene triplications in beta-thalassemia in Asian Indians and its effect on phenotype, which was the primary aim of this study. Gap-PCR was performed in order to detect common alpha thalassemia determinants (-alpha(3.7), -alpha(4.2) and alpha alpha alpha(anti 3.7) triplication). Alpha-triplication was detected in 15.4% (10/65) of patients with thalassemia intermedia, 8.8% (4/45) of those with thalassemia minor and in 2.7% (2/74) of healthy controls. The severity of jaundice was higher in thalassemia intermedia cases with alpha-triplication and two of the alpha-triplication cases had a marked increase in serum bilirubin following intercurrent illness. Thus, alpha globin gene triplication is important genetic determinant underlying thalassemia intermedia in North Indians. Patients with alpha-triplication may develop prominent jaundice with marked increase in serum bilirubin following antecedent aggravating factors.

Adolescent↗
PubMed1999

Iron release in erythrocytes from patients with beta-thalassemia.

Our previous studies have shown that iron is released in a free (desferrioxamine-chelatable) form when erythrocytes undergo oxidative stress (incubation with oxidizing agents or aerobic incubation in buffer for 24-60 h (a model of rapid in vitro ageing)). The release is accompanied by oxidative alterations of membrane proteins as well as by the appearance of senescent antigen, a signal for termination of old erythrocytes. In hemolytic anemias by hereditary hemoglobin alterations an accelerated removal of erythrocytes occurs. An increased susceptibility to oxidative damage has been reported in beta-thalassemic erythrocytes. Therefore we have investigated whether an increased iron level and an increased susceptibility to iron release could be observed in the erythrocytes from patients with beta-thalassemia. Erythrocytes from subjects with thalassemia intermedia showed an extremely higher content (0 time value) of free iron and methemoglobin as compared to controls. An increase, although non-statistically-significant, was seen in erythrocytes from subjects with thalassemia major. Upon aerobic incubation for 24 h the release of iron in beta-thalassemic erythrocytes was by far greater than in controls, with the exception of thalassemia minor. When the individual values for free iron content (0 time) seen in thalassemia major and intermedia were plotted against the corresponding values for HbF, a positive correlation (P < 0.001) was observed. Also, a positive correlation (P < 0.01) was seen between the values for free iron release (24 h incubation) and the values for HbF. These results suggest that the presence of HbF is a condition favourable to iron release. Since in beta-thalassemia the persistance of HbF is related to the lack or deficiency of beta chains and therefore to the excess of alpha chains, the observed correlation between free iron and HbF, is consistent with the hypothesis by others that excess of alpha chains represents a prooxidant factor.

Adult↗
PubMed1990

Interferon-gamma modulates fetal hemoglobin synthesis in sickle cell anemia and thalassemia.

Interferon-gamma (IFN-gamma) has been shown to influence globin gene expression in cord blood and normal adult progenitor-derived erythroblasts. To explore the influence of IFN-gamma on fetal hemoglobin (HbF) synthesis in the hemoglobinopathies, erythroid progenitors (BFU-E, burst forming unit-erythroid) from patients with sickle cell anemia (SCA) and thalassemia were co-cultured with or without IFN-gamma. Hemoglobin content in progenitor-derived erythroblasts was assessed by radioligand assay (RIA). Co-culture of erythroid progenitors from 12 SCA patients with 200-400 U/ml of IFN-gamma resulted in a significant decrease in picograms of HbF and percent HbF per BFU-E-derived erythroblast. The mean decrease (+/- SEM) of picograms of HbF per cell and percent of HbF was by 42 +/- 9% and 35 +/- 8% of control cultures, respectively. Co-culture of erythroid progenitors from 10 patients with thalassemia major or thalassemia variant (HPFH/thalassemia, sickle/beta 0-thalassemia) with 200 U/ml IFN-gamma also resulted in a significant decrease in picograms and percent of HbF per BFU-E-derived erythroblast. IFN-gamma treatment also inhibited the enhancement in gamma-globin synthesis induced in culture by butyric acid. Erythroid progenitors from 2 patients with SCA, 1 patient with sickle/beta 0-thalassemia, and 1 patient with HbE/beta 0-thalassemia were co-cultured with IFN-gamma, L-alpha-amino-n-butyric acid, or both. HbF content (expressed as picograms HbF/cell) was decreased in samples co-cultured with IFN, increased in cultures with L-alpha-amino-n-butyric acid, but remained at control values in cultures treated with IFN plus L-alpha-amino-n-butyric acid. These data demonstrate that IFN-gamma is an environmental factor that influences gamma-globin gene expression in the beta hemoglobinopathies in vitro.

Aminobutyrates↗
PubMed2006

Validity assessment of nine discriminant functions used for the differentiation between iron deficiency anemia and thalassemia minor.

Iron deficiency anemia (IDA) and thalassemia minor are two of the most common causes of microcytic anemias worldwide. Because of similar red blood cell count parameters and blood picture, it was imperative to develop other measures that would differentially and correctly diagnose these two anemias. Several mathematical formulas and simple RBC indices have been introduced as simple, fast and inexpensive means of providing differential diagnosis for IDA and thalassemia minor. The Objective of this study was to apply and compare nine well-documented discriminant functions on a population of 153 confirmed cases of microcytic anemias (IDA n = 56, beta-thalassemia minor n = 47 and alpha-thalassemia n = 50) and to measure validity using Youden's Index. The results show that England and Fraser (E & F) Index had the highest Youden's Index value (98.2) in correctly differentiating between IDA and alpha- and beta-thalassemia minor, while Shine and Lal Index was found ineffective in differentiating between microcytic anemias in our population. E & F Index showed with great sensitivity and specificity to be the best discriminant function to differentiate between IDA and thalassemia minor cases.

Anemia, Iron-Deficiency↗
PubMedDate not supplied

Few reports of hemoglobin E/beta-thalassemia in Northeast India: underdiagnosis or complete exclusion of beta-thalassemia by hemoglobin E.

PURPOSE: India bears a major burden of homozygous beta-thalassemia. Hemoglobin (Hb) E/beta-thalassemia has been described mainly among Bengalis in Eastern India. Ethnic groups in northeastern India have among the highest known gene frequency for Hb E. However, there are few reports of Hb E/beta-thalassemia from these ethnic groups. This study aims to determine whether the paucity of reports of Hb E/beta-thalassemia from this region are because of underdiagnosis or complete elimination of beta-thalassemia by Hb E. POPULATIONS AND METHODS: The published literature concerning Hb E, beta-thalassemia, and the syndrome of Hb E/beta-thalassemia in Indid, Tibeto-Burman, and Austro-Asiatic ethnic groups in northeast India was analyzed to determine the gene frequency of Hb E and beta-thalassemia for different ethnic groups. The expected cases of Hb E/beta-thalassemia were calculated using the Hardy-Weinberg law. RESULTS: The Bodo-Kachari have a gene frequency of 0.50 for Hb E, the highest anywhere in the world. There are, however, no reports of beta-thalassemia in this group. Among ethnic groups in which prevalence of Hb E and beta-thalassemia are known, there is a vast discrepancy between the reported number of cases of Hb E/beta-thalassemia and the number predicted by Hardy-Weinberg law. Thus, there are only seven cases of Hb E/beta-thalassemia from northeast India reported in the literature as opposed to 67,332 predicted cases. CONCLUSION: A potentially large pool of unsuspected Hb E/beta-thalassemia cases exist in northeast India. The significance of this finding and possible contributory factors are discussed.

Demography↗
PubMedDate not supplied

Infections in E-beta thalassemia.

Infection is a major complication and the leading cause of death in thalassemia, especially E-beta thalassemia. The spectrum of infections in E-beta thalassemia include mild and severe infections, therapy-related infections such as Yersinia enterocolitica infection associated with desferrioxamine (DFO) therapy, and transfusion-transmitted disease, as well as unique infections such as with pythiosis. Prospective studies in Thailand indicate that patients with E-beta thalassemia had more frequent episodes of both mild and severe infections. The former included upper respiratory tract infection, acute gastroenteritis, cutaneous abscess, and gingivitis. Severe infections occurred more commonly in patients with splenectomy and included septicemia, pneumonia, biliary tract infection, salmonellosis, and urinary tract infection. Responsible organisms were Escherichia coli (26%), Klebsiella pneumoniae (23%), Salmonella (15%), and Streptococcus pneumoniae (13%). Other organisms included Pseudomonas, Staphylococci, Burkholderia pseudomallei (melioidosis), and Aeromonas. Patients undergoing DFO therapy are at risk for Y. enterocolitica infection which may be localized to mesenteric nodes and tonsils or occur as a generalized form such as septicemia. Recently, we have seen a unique infection so-called vascular pythiosis. Patients usually presented with clinical features of vascular occlusion of lower limbs from ascending arteritis and thrombosis. The causative organism, Pythium insidiosum, is fungus-like, in the kingdom Stramenopila, and in the class Oomycetes. The mortality rate is high and the only effective treatment has been early amputation or possibly immunotherapy. The predisposing factors of infections in thalassemia include splenectomy, iron overload, anemia, and granulocyte dysfunctions. General management of infections in thalassemia consist of prevention, i.e., immunization with pneumococcal and hepatitis vaccines, oral penicillins especially in patients with splenectomy, removal of predisposing factors such as gallstones, iron overload, and appropriate antibiotics.

Bacterial Infections↗
PubMed2003

Techniques and clinical outcomes of laparoscopic cholecystectomy in adult patients with beta-thalassemias.

Beta-thalassemia, which results from a reduced production of beta-globin chain of hemoglobin, is a common single gene disorder with an extremely heterogeneous clinical picture. Its presentation may vary from mild anemia in beta-thalassemia minor to severe and life-threatening anemia in beta-thalassemia major. Recent advances in supportive treatment of beta-thalassemia major have resulted in substantial increase in survival in these patients, and an increasing number of these patients reach adolescence and adulthood. The incidence of cholelithiasis is reported to be increased in these patients. Although laparoscopic cholecystectomy (LC) has become the gold standard treatment of symptomatic gallstone disease, its experience in adult beta-thalassemic patients has been limited. From May 1992 through April 2000, 10 consecutive adult beta-thalassemic patients with symptomatic gallstone underwent LC at our institution. Data were obtained on the type of beta-thalassemia, presentation, preoperative laboratory findings, history of preoperative transfusion, postoperative complications, postoperative analgesic requirement, length of hospital stay, and follow-up. All operations were completed laparoscopically. The mean operative time was 98.5 minutes. The postoperative analgesic requirement was minimal. There was no mortality. One patient developed fever postoperatively due to lung atelectasis that was managed conservatively. The mean hospital stay was 3 days. Laparoscopic cholecystectomy is feasible, safe, and effective in the treatment of adult beta-thalassemic patients with symptomatic gallstone disease. Technical adjustments are required when operating on patients with beta-thalassemia major.

Adult↗
PubMed2005

Renal tubular function in children with beta-thalassemia minor.

BACKGROUND: beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. METHODS: The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) </= 11 g/dL) (Group 1, n = 14) and non-anaemic (Hb > 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. RESULTS: There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). CONCLUSION: On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

Acetylglucosaminidase↗
PubMed1984

The molecular and hematological heterogeneity of alpha thalassemia.

A study of genotypes in alpha thalassemia and their corresponding hematological phenotypes has shown that alpha(+) thalassemia is the most frequent type encountered in a Sydney population. Phenotypes of heterozygous alpha(+) thalassemia (alpha alpha/-alpha) in adults or children differ little from normal and so the disorder is difficult to identify. In contrast, Hb Bart's (gamma 4) is a useful marker for alpha alpha/-alpha in cord blood samples. Abnormal phenotypes are present in homozygous alpha(+) thalassemia (-alpha/-alpha), heterozygous alpha(0) thalassemia (alpha alpha/--) and non-deletional alpha thalassemia. Therefore, detection by routine hematological studies should be possible. A less severe phenotype in -alpha/-alpha compared to alpha alpha/-- was found which is interesting since 2 alpha globin genes are lost in both instances.

Adult↗
PubMed2005

Heterogeneity in alpha-thalassemia interactions in Malays, Chinese and Indians in Malaysia.

AIM: Interactions between different determinants of alpha-thalassemia raises considerable problems, particularly during pregnancies where antenatal diagnosis is necessary. This study aims to determine the different types of deletional alpha-thalassemia and Hemoglobin Constant Spring (HbCS), and their frequency in Malays, Chinese and Indians in Malaysia. METHODS: DNA from 650 pregnant women from the Antenatal Clinic of the University of Malaya Medical Center in Kuala Lumpur, Malaysia who showed mean cell volume < or =89 fL and/or mean cell hemoglobin < or =28 pg were analyzed for the double alpha-globin gene South-East Asian deletion (--SEA), the -alpha3.7 and -alpha4.2 single alpha-globin gene deletions and HbCS. RESULTS: One hundred and three (15.8%) of the pregnant women were confirmed as alpha-thalassemia carriers: 25 (3.8%) were alpha-thalassemia-1 carriers with the --SEA/alphaalpha genotype, 64 (9.8%) were heterozygous for the -alpha3.7 rightward deletion (-alpha3.7/alphaalpha), four (0.6%) were heterozygous for the -alpha4.2 leftward deletion (-alpha4.2/alphaalpha), nine (1.4%) were heterozygous for HbCS (alphaCSalpha/alphaalpha) and one (0.2%) was compound heterozygous with the -alpha3.7/alphaCSalpha genotype. The double alpha-globin gene --SEA deletion was significantly higher in the Chinese (15%) compared to the Malays (2.5%) and not detected in the Indians studied. The -alpha3.7 deletion was distributed equally in the three races. HbCS and -alpha4.2 was observed only in the Malays. CONCLUSION: The data obtained gives a better understanding of the interactions of the different alpha-thalassemia determinants in the different ethnic groups, thus enabling more rapid and specific confirmation of alpha-thalassemia in affected pregnancies where antenatal diagnosis is necessary.

Adolescent↗
PubMed1980

Prenatal diagnosis of beta thalassemia: experience with 133 cases and the effect of fetal blood sampling on child development.

Prenatal diagnosis was attempted in 133 pregnancies at risk for beta thalassemia (132 cases) or sickle-cell beta 0 thalassemia (1 case). Of these, 76 couples requested diagnosis because they already had children affected with homozygote beta thalassemia (72 cases) or beta+ thalassemia (4 cases). The others were probably at risk for beta 0 thalassemia since this is by far the predominant thalassemia type in Sardinia. Sufficient fetal blood for analysis was obtained by placental aspiration at 18--24 weeks gestation in 130 cases. Ten fetal losses occurred. The pregnancies were followed and no relevant complications were seen. Of the newborns delivered, 45 were followed from birth with particular attention to congenital malformation, neurological, growth, and maturity assessement. No major adverse effect of placentocentesis on child growth and development was observed. Placental samples were analyzed by globin chain synthesis analysis on carboxylmethylcellulose columns. When the placental samples contained more than 20% maternal red cells, fetal red cell enrichment was carried out by anti-i (53 cases) or anti-AB (2 cases) differential agglutination or NH4Cl-NH4HCO3 differential lysis of maternal cells (17 cases). Of the 130 cases, 32 fetuses had no beta-chain radioactivity and one had a beta/gamma ratio of 0.005. These were presumed to be homozygous and all but one were electively aborted. Absence of beta-chain radioactivity was confirmed in 10 abortuses with suitable cord blood samples. A total of 91 infants have been born and are nonhomozygous. Genotype assessment at 6 months after birth in 33 infants showed that there was only a slight overlap between the ranges of normal (0.095 +/- 0.016) and heterozygous (0.05 +/- 0.01) fetal beta/gamma globin chain synthesis ratios.

Blood Specimen Collection↗
PubMed1980

Hemoglobin F in beta thalassemia and related conditions.

Further examination of the Hb F in beta thalassemia has substantiated earlier conclusions that the Hb F of heterozygotes has a bimodal distribution of the G gamma to A gamma ratio whereas that of homozygotes does not. Although the T gamma chain is present in the Hb F of beta thalassemia and delta beta thalassemia, it occurs also in cord blood Hb F without thalassemia and it, therefore, is not a special feature of the thalassemia condition. The T gamma chain has not been detected in the Hb F from HPFH. Because studies of genomic DNA have detected single G gamma and A gamma genes instead of pairs of both, some explanations of the observed heterogeneity and control of Hb F production must be reconsidered. On the other hand, experiments with DNA agree with the suggestion that a different extent of deletion leads to HPFH or to delta beta thalassemia. As further studies of genomic DNA are made, a search should be made for the means by which the G gamma to A gamma ratio is controlled at the newborn or adult level, for the manner in which the quantity of Hb F is regulated, and for the determinants that may influence the production of Hb F in trans.

Chromosome Deletion↗
PubMed1990

Beta-thalassemia intermedia in Turkey.

DNA data have been collected for 41 patients with beta-thalassemia intermedia without transfusion dependency. They belonged to 33 families, and 45 of their parents were included in the study. Eight patients were homozygous for the frameshift at codon 8 (-AA), and nine were homozygous for the IVS-2 nt 1 (G----A) mutation; haplotypes IV and III, respectively, were associated with these mutations. Three patients had a G gamma A gamma(delta beta)0-thalassemia homozygosity, characterized by a deletion of 13 kb. Of the remaining subjects, ten had a homozygosity for the IVS-1 nt 6 (T----C) mutation, and five were compound heterozygotes for one mild and one severe thalassemia determinant. Combinations with Hb Knossos, the T----A mutation at nt -30, the C----T mutation at nt -101, the G----A and G----C mutations at IVS-1 nt 5, and the G----A mutation at IVS-1 nt 110 were the other thalassemia determinants resulting in beta-thalassemia intermedia in the six remaining patients. Haplotypes IV and IX were associated with the latter three mutations. The C----T mutation at nt -158 5' to the G gamma gene was characteristic for haplotypes III, IV, and IX. Genotype and phenotype correlation indicated significant differences in some of the hematological parameters among patients with the frameshift at codon 8 (-AA) or with the IVS-2 nt 1 (G----A) mutation, with both the frameshift at codon 8 and the T----C mutation at IVS-1 nt 6, and with both the IVS-2 nt 1 (G----A) and IVS-1 nt 6 (T----C) mutations. Statistically significant differences were found in the mean values for hemoglobin (Hb) A2 in heterozygotes with the frameshift at codon 8 (-AA) and the IVS-1 nt 5 (G----A) mutation. Variations in the number of alpha-globin genes resulted in modifications of the phenotypical expression of the beta-thalassemia intermedia determinants.

Chromosome Deletion↗
PubMed1990

Antenatal diagnosis of beta-thalassemia in Sardinia.

This paper reviews the characteristics and the results of 15 years of experience with a preventive program, based on carrier screening and prenatal diagnosis, designed to control thalassemia major in the Sardinian population. The education of the population about thalassemia and the modalities for its prevention was accomplished via the mass media. Carrier screening was carried out voluntarily on couples of child-bearing age. Prenatal diagnosis was initially carried out by fetal blood analysis; since 1983, it has been done by DNA analysis on non-amplified or amplified DNA. Different chorionic villous sampling procedures have been used. Nowadays, we have adopted the transabdominal approach because, in our experience, it seems to be associated with a low risk (2%) of fetal mortality. At the present time, the beta-thalassemia mutations are detected directly by dot-blot analysis of amplified DNA with 32P- or horseradish peroxidase-labeled allele-specific oligonucleotide probes. Two oligonucleotide probes, one complementary to the codon-39 nonsense mutation, which accounts for 95.7% of the beta-thalassemia chromosomes in the Sardinian population, and the other complementary to the frameshift at codon 6, which is the second most common mutation in our population (2.1%), allow us to make prenatal diagnosis in the large majority of cases. Notwithstanding a careful dissection of maternal decidua from chorionic villi, co-amplification of maternal sequence was detected in 4 out of 425 cases tested by this procedure. In order to avoid this pitfall, the simultaneous amplification of highly polymorphic VNTR (variable number of tandem repeats) segments could be used. On the whole we have so far carried out 2711 prenatal tests: 1130 by fetal blood analysis, 1156 by oligonucleotide hybridization on electrophoretically separated DNA fragments, and 425 by dot-blot analysis on amplified DNA with allele-specific oligonucleotide probes. Two errors occurred by fetal blood analysis and none by DNA analysis. The incidence of thalassemia major declined from 1:250 live births in the absence of prevention to 1:1000 after the establishment of this program, indicating that carrier screening and prenatal diagnosis are effective means for preventing thalassemia major at the population level.

Female↗
PubMed1998

The role of recombinant human erythropoietin in the treatment of thalassemia.

The rationale for treatment with recombinant human erythropoietin (rHuEPO) in thalassemia came from studies in baboons, thalassemic mice and in erythroid cultures. The results demonstrated an increase in gamma globin synthesis and consequently in fetal Hb (Hb F) resulting in improvement in erythropoietic parameters. In addition, endogenous serum Epo levels in various forms of thalassemia were inconsistent and not related to the severity of the anemia. Therefore, several preliminary studies with rHuEPO were performed, mainly on patients with beta thalassemia intermedia. The results indicate: a) a significant, dose-related (500 u/kg to 1000 u/kg x 3/week) increase in thalassemia erythropoiesis without changes in % of Hb F, MCV and MCH, mainly in splenectomized patients; b) the minimum effective dose is 500 u/kg x 3/week; c) there were no major side effects during the continuous treatment period of 9 months. In order to improve both quantitative and qualitative thalassemia erythropoiesis, several trials were undertaken combining rHuEPO with hydroxyurea (HU), which is known to increase % Hb F, MCV and MCH without a major effect on Hb levels. The designed trial included 3 to 6 months of HU alone (20 mg/kg x 4/week), or with rHuEPO alone (500 u/kg x 3/week or 375 u/kg x 2/week) or a combination of the two drugs. The results show an additive effect of the two drugs, in some of the patients. It is not known whether the addition of oral iron to rHuEPO is warranted for maximal erythropoietic response. The major limiting factor in designing large scale clinical trials is the relatively high cost of the drug. Nevertheless rHuEPO alone or in combination with other Hb F modulating drugs may have a positive effect in thalassemia with resulting improvement in the quality of life.

Animals↗