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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell disease (SCD), the commonest single gene disorder worldwide, is an inherited disease that has different clinical and hematological manifestations in different populations. The objective of this study is to describe the characteristics of the Lebanese SCD population. This was a retrospective study that included information on 387 patients with either sickle cell anemia (SS) or sickle beta-thalassemia (ST). The mean (+/-SD) age was 17.9 years (+/-12.5), and the mean (+/-SD) follow-up was 9.3 +/- 6.9 years. Fifty percent of the patients were males and SS/ST distribution was 3 : 1. The disease was clustered in two geographic areas in North and South Lebanon. Nearly, all patients were Muslims and 56% were the offspring of consanguineous parents. The prevalence of splenomegaly beyond 6 years of age among SS patients was 28.9%. The prevalence rates of stroke, leg ulcers and priapism were 4.1%, 1.4%, and 0.8%, respectively. Comparing the SS and the ST patients, there were no statistically significant differences in the prevalence of all clinical manifestations except for splenomegaly (SS: 28.9%, ST: 54.9%, P-value < 0.001) and splenectomy (SS: 16.1%, ST: 35.7%, P-value < 0.001). In contrast to Northern American populations and similar to some Mediterranean populations, Lebanese SCD patients have a higher prevalence of persistent splenomegaly. The relatively low incidence of thrombotic complications deserves further investigation. The study's limitations include those of any other retrospective study and the fact that not all Lebanese centers caring for inherited hemoglobin disorders were included. However, the results of this first large scale national survey indicate that preventive efforts should target the Northern and Southern regions of Lebanon to decrease the number of new off springs afflicted with this disease similar to what has been successfully achieved with Thalassemia, another hemoglobinopathy that is highly prevalent in the country.
Int J Lab Hematol 2007 Dec
PMID:Sickle cell disease: the Lebanese experience. 1798 93

Newborn screening tests are designed to detect infants with specific conditions whose families also benefit from early diagnosis and treatment. These conditions include disorders of metabolism, endocrinopathies, hemoglobinopathies, hearing loss, and cystic fibrosis. Each state program must have a system in place for notification, timely follow-up, and evaluation of any infant with a positive screening result. Newborn screening programs have enormous public health benefits and have been effective in identifying newborns that can benefit from early treatment.
Obstet Gynecol 2007 Dec
PMID:ACOG Committee Opinion No. 393, December 2007. Newborn screening. 1805 55

Recent evidence from a large, randomized, controlled trial has suggested that the universal administration of iron to children in malaria-endemic areas is associated with an increase in adverse health outcomes. The purpose of this paper is to summarize the available ecologic and intervention trials related to iron and malaria in children, and to set these against current knowledge of the biology of host-pathogen interactions involving iron metabolism. We conclude that, although not fully consistent, the balance of evidence confirms that administration of iron (usually in combination with folic acid) increases the incidence of malaria when given without prophylaxis and in the absence of universal access to treatment. The mechanisms by which additional iron can benefit the parasite are far from clear. There is evidence to suggest that the apparent detrimental effect of iron supplementation may vary according to levels of antecedent iron status, the presence of hemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD) deficiency, and other host genetic variants, such as variants in haptoglobin. The effects of malaria on host iron metabolism are also reviewed and reveal that the key cause of malaria-induced anemia is a maldistribution of iron and suppression of erythropoiesis rather than an exacerbation of gross iron deficiency. We tentatively conclude that, if it is to be recommended, universal iron supplementation in malarious areas should only be considered in conjunction with some form of prophylaxis (e.g., intermittent preventive therapy [IPT]) or in the context of good health services with ready access to facilities for malaria diagnosis and treatment. An alternative approach would be to screen for anemia and target supplementation only to anemic children. With regard to treatment, there is good evidence that iron supplementation should be withheld until the treatment schedule is complete, both because iron may inhibit treatment and because the absorption of oral iron is blocked by the inflammatory response.
Food Nutr Bull 2007 Dec
PMID:Iron metabolism and malaria. 1829 91

To improve the differentiation of thalassemia intermedia from other hemoglobinopathies in Iran, four known genetic mechanisms-XmnI (G)gamma polymorphism, inheritance of mild and silent beta-thalassemia alleles, delta beta deletion, and coinheritance of alpha- and beta-thalassemia-were investigated in 52 Iranian individuals suspected to have thalassemia intermedia based on clinical and hematological characteristics. Beta-globin mutations were studied using a reverse-hybridization assay and sequencing of the total beta-globin gene. The XmnI (G)gamma polymorphism, the Sicilian delta beta deletion, and four alpha-globin mutations (-a(3.7), -a(4.2), -(MED), aaa(anti-3.7)) were studied using PCR-based techniques. The inheritance of the XmnI (G)gamma polymorphism with severe beta-thalassemia alleles in the homozygous or compound heterozygous state was the predominant mechanism observed in 27 individuals (55.3%). In five cases, this status overlapped with the -a(3.7)/aa genotype. The second most frequent cause for thalassemia intermedia (14.8%) was the inheritance of mild beta-thalassemia alleles, including IVS-I-6 (T > C), -88 (C > A), and + 113 (A > G). In three subjects (4.3%) the Sicilian delta beta deletion was identified. HbS in association with beta-zero-thalassemia was found in three patients with thalassemia intermedia phenotype. In 11 cases (21.3%) no causative genetic alteration could be identified. Our results reflect the diversity underlying thalassemia intermedia, and the limitations of the applied clinical, hematological, and molecular approaches for correct diagnosis. Some of the unresolved cases will offer an opportunity to discover additional molecular mechanisms leading to thalassemia intermedia.
Genet Test 2008 Dec
PMID:Molecular mechanisms underlying thalassemia intermedia in Iran. 1893 39

The authors have studied the interactions of intact hemoglobin mixtures of HbE and HbA, with the major erythroid membrane skeletal protein, spectrin and tailor-made phospholipids membranes containing aminophospholipids to understand the role of spectrin and phospholipids of erythrocytes in the overall pathophysiology of the hemoglobin disorders. Hemoglobin mixtures were isolated and purified from the peripheral blood samples of HbE carriers and different HbEbeta thalassemia patients, taken for diagnosis. Spectrin binding was studied by fluorescence and oxidative crosslinking, by SDS-PAGE. Membrane perturbation experiments were carried out to study the leakage of the self-quenching fluorophore, carboxyfluorescein, entrapped in the phospholipid vesicles. Hemoglobin mixtures with elevated levels of HbE showed stronger interactions with spectrin reflected in the decrease in binding dissociation constant from 17 to 5 muM upon increase in HbE% from about 30 to 90% in the hemolysates. The yield of the spectrin crosslinked complexes of such hemoglobin mixtures also increased with increase in HbE levels. Presence of ATP/Mg and DPG were found to decrease the overall yield of such complexes and the binding affinity of hemoglobins to spectrin. HbE rich hemolysates also induced greater leakage of entrapped carboxyfluorescein (CF) from phospholipid membranes containing aminophospholipids. Results from this study indicate the roles of skeletal proteins and aminophospholipids, particularly under oxidative stress conditions to be important in the premature destruction of erythrocytes in hemoglobin disorders, e.g. HbEbeta-thalassaemia.
Hematology 2008 Dec
PMID:Oxidative crosslinking, spectrin and membrane interactions of hemoglobin mixtures in HbEbeta-thalassemia. 1905 66

Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here, we examine BCL11A as a potential regulator of HbF expression. The high-HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders.
Science 2008 Dec 19
PMID:Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. 1909 32

Fever of unclear origin is a clinical challenge in medical practice. Infectious diseases, neoplasms, and collagen vascular illnesses are its main causes in adults and children. Acute splenic sequestration crises, a known potentially fatal complication of sickle cell disease and sickle beta-thalassemia, are uncommon in beta-heterozygosis. We describe a case of prolonged recurrent episodes of fever with spontaneous resolution, commencing at age 10 in a 15-year-old boy with a history of hypochromic microcytic anemia attributed to a thalassemic trait. He was admitted twice to our university hospital for continuous-remittent fever with a pruritic, macular evanescent Still's skin rash, severe splenomegaly, leucopenia, thrombocytopenia, and sudden aggravation of anemia. Infectious, rheumatologic, autoimmune, and hematologic illnesses were excluded. A genetic-based study revealed heterozygosis of the beta-globin gene for a A>C (Thr>Pro) substitution at position 87 called Hemoglobin Valletta (alpha 2 beta 2 87 PRO) with a C>G transition in homozygosis in beta-globin intronic polymorphism intervening sequence 2 at nucleotide 745. After a follow-up period of 1 year without treatment, the young patient remains apyretic and in good general clinical health with persistent microcythemia and hepatosplenomegaly. Acute splenic sequestration crisis and related cytopenia may be an unusual complication of fever of unclear origin in a beta-thalassemic carrier of a Hemoglobin Valletta mutation and polymorphism in homozygosis of intervening sequence 2 at nucleotide 745. This hemoglobinopathy may predispose to a clinical phenotype of minor or intermediate thalassemia and, during a febrile illness, to hemoglobin instability and splenic sequestration.
Am J Med Sci 2008 Dec
PMID:Fever of unclear origin and cytopenia because of acute splenic sequestration in a young immunocompetent carrier of beta-globin mutation for Hb Valletta. 1909 26

Glycohemoglobin (HbA1c) estimation is the gold standard for assessing long-term glycemic control in diabetic patients. Some hemoglobin variants interfere with HbA1c assay, thus, limiting its utility. Over 150,000 diabetic patients are estimated to have hemoglobin variants in the United States; but this number may be up to 30% in some parts of the world. Although, most of the hemoglobinopathies are clinically silent, some of them cause biochemical aberrations, which could interfere with HbA1c assay. However, hemoglobin N-Baltimore has not been reported to give false HbA1c estimation. We present a woman with mistaken diagnosis of diabetes due to hemoglobin N-Baltimore that produced a spuriously elevated HbA1c level.
Am J Med Sci 2008 Dec
PMID:A mistaken diagnosis of type 2 diabetes due to hemoglobin N-Baltimore. 1909 30

Sickle cell disease is a genetic hemoglobinopathy in which a significant number of red blood cells carry hemoglobin-S as opposed to normal red blood cells that contain hemoglobin-A. Under certain conditions such as hypoxia, acidosis, and hypothermia, the red blood cells containing hemoglobin-S will sickle, leading to occlusion of the microvasculature. As such, patients with sickle cell disease present unique challenges during heart surgery using cardiopulmonary bypass (CPB). After conducting a literature review, we discovered that the exact hemoglobin-S level for conducting cardiac surgery with CPB is not known. However, a hemoglobin-S level < 30% is considered safe for conducting CPB. The following case report will discuss these challenges and present a patient with sickle cell disease undergoing a mitral valve repair. Management of this patient involved exchange transfusions both preoperatively and intraoperatively.
J Extra Corpor Technol 2008 Dec
PMID:Mitral valve replacement in a patient with sickle cell disease using perioperative exchange transfusion. 1919 58

Haemoglobinopathies are a series of hereditary genetic diseases which, if left untreated, usually prove fatal. The present paper discusses how one of the most important of these, beta-thalassaemia, afflicted the island of Cyprus in the last century and almost threatened to eliminate the whole population. In narrating the medical facts of the disease we point out the moral dilemmas which medical personnel, the state and the church had to deal with before they embarked on a program for the treatment and prevention of beta-thalassaemia. After careful study of the program we conclude that, although in the given case it proved a successful model for the management of beta-thalassaemia, it bears no resemblance whatsoever to eugenics.
Med Law 2008 Dec
PMID:The experience of beta-thalassaemiaand its prevention in Cyprus. 1763 52


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