Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0039730 (thalassemia)
10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Management of thalassemia major has shown substantial clinical and prognostic improvement, suggesting the need for major attention to quality of life. We studied bone health in 25 patients (13 males, 12 females; 15-23 years old) affected by beta-thalassemia major. In all patients, bone mineral density (BMD), biochemical markers of bone and calcium metabolism (calcium, phosphate, magnesium, alkaline phosphatase, urinary calcium, 25-hydroxyvitamin D [25OH-D], 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone [PTH]), hematological parameters and gonadal steroids status were assessed and related to each other and to auxological parameters (chronological, statural and bone ages, height, weight, stage of puberty). BMD of the lumbar spine (L1-L4) (g/cm2) and expressed as Z-scores, was assessed by dual energy X-ray absorptiometry. PTH levels were low in seven patients (28%), and in the normal range in 18 (72%). 25OH-D serum levels were normal in 16 patients (64%) and low in nine (36%). 1,25(OH)2D values were reduced in 19 patients (76%) and normal in six (24%). Alkaline phosphatase correlated with bone age delay (r = 0.414; p = 0.039); no other statistically significant correlation was found. Mean BMD values in patients with thalassemia were significantly reduced in comparison with that of age- and sex-matched controls (Z-score: -2.8 +/- 2.0, p <0.001; -3.3 +/- 2.1 in males, and -2.2 +/- 1.9 in females). Twenty-one patients (84%) showed reduced BMD. Overall, BMD reduction was in the osteopenia range in five patients (20%) and in the osteoporosis range in 16 patients (64%). Our data indicate that low BMD is often present in patients with thalassemia, although recognized late, as in the present series. Early diagnosis should be done during childhood, in order to improve the quality of life in adulthood.
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PMID:Effects of thalassemia major on bone mineral density in late adolescence. 1272 13

beta-Thalassemia, an inherited blood disorder, mainly affects people from the Mediterranean region. This life-threatening anemia is so severe that regular blood transfusions and iron-chelating therapy is obligatory throughout life. Commonly occurring complications, especially in adult patients, are osteopenia and osteoporosis. Osteoporotic fractures are strongly associated with bone density, which is under polygenic control. Type I collagen, which is encoded by the COLIA1 and COLIA2 genes, is the major protein in the bone. A G-->T polymorphism in the regulatory region of the COLIA1 gene at a recognition site for transcription factor Sp1 has been strongly associated with osteoporotic fractures. In this study, the G-->T polymorphism is screened in 42 beta-thalassemia major and 10 beta-thalassemia intermedia patients. 64.3% of the beta-thalassemia patients were heterozygotes for G/T (Ss) polymorphism and 35.7% were homozygous for G/G (SS), 60% of the beta-thalassemia intermedia patients were heterozygous (Ss) and 40% were homozygous (ss). The number of heterozygotes in the beta-thalassemia major group was significantly higher, compared to the control group (F = 13.615, P = 0.001). The number of heterozygotes in beta-thalassemia intermedia group was also significantly higher, compared to the control group (F = 5.158, P = 0.029). Patients who are G/T heterozygotes (Ss) at the polymorphic Sp1 site have a lower bone mineral density than G/G homozygotes (SS) (P = 0.01).
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PMID:Polymorphism analysis in the COLIA1 gene of patients with thalassemia major and intermedia. 1280 21

ABSTRACT : BACKGROUND : The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS : Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS : Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 +/- 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION : High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.
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PMID:Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. 1291 70

Thalassemia/hemoglobinopathy is a hereditary disease that causes chronic anemia and increased erythropoiesis. Consequently, an expansion of bone marrow spaces may contribute to osteopenia/osteoporosis. However, the pathogenesis of bone changes is not yet known. We, therefore, carried out the study on bone histomorphometry and biochemical and hormonal profiles in children and adolescents with suboptimally treated beta-thalassemia disease with the hope of gaining some new insight into the cellular and structural alterations of thalassemic bone. Seventeen patients underwent iliac crest bone biopsy for histomorphometric analyses. Bone mineral density (BMD) measurements were performed by dual energy x-ray absorptiometry. Most patients had growth retardation and delayed bone age. BMD was low especially at the lumbar spine. Serum IGF-I levels were almost always low. Bone histomorphometry revealed increased osteoid thickness, osteoid maturation time, and mineralization lag time, which indicate impaired bone matrix maturation and defective mineralization. In addition, iron deposits appeared along mineralization fronts and osteoid surfaces. Moreover, focal thickened osteoid seams were found together with focal iron deposits. Dynamic bone formation study revealed reduced bone formation rate. These findings indicate that delayed bone maturation and focal osteomalacia are the pathogenesis of bone disease in suboptimally blood-transfused thalassemics with iron overload. Iron deposits in bone and low circulating IGF-I levels may partly contribute to the above findings.
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PMID:Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. 1291 94

Osteoporosis in beta-thalassaemia is multifactorial; increased osteoclast function seems to play an important role in its pathogenesis. The aim of this study was to evaluate the effect of pamidronate on the osteoporosis of thalassaemia. To this effect we studied 26 patients who received this drug in doses of 30 or 60 mg i.v. once a month over 12 months. The effects were monitored by measuring bone mineral density (BMD) in association with markers of osteoclast function [soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG)] and of bone remodelling [N-telopeptide of collagen type-I (NTX), tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), bone-alkaline phosphatase (bALP), and osteocalcin (OC)]. Thirty healthy individuals were also studied, as controls. NTX, TRACP-5b, bALP and OC levels were significantly higher in thalassaemic patients compared with controls; in contrast, OPG levels were significantly lower, while the levels of sRANKL varied within normal limits. Administration of pamidronate was followed by a clear decrease of NTX, TRACP-5b, OPG, and OC, and by a significant increase in the BMD of the lumbar spine, which was similar in patients of both treatment groups. These data suggest that pamidronate, at a monthly dose of 30 mg, is an effective treatment for thalassaemic osteoporosis.
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PMID:Pamidronate is an effective treatment for osteoporosis in patients with beta-thalassaemia. 1501 77

Osteoporosis represents an important cause of morbidity in adult patients with thalassaemia major (TM). The pathogenesis of osteoporosis in TM is multifactorial, and includes bone marrow expansion, endocrine dysfunction and iron overload. Additional genetic factors, such as the COLIA 1 gene polymorphism, seem to play an important role in the development of low bone mass in these patients. However, the mechanisms through which these factors lead to bone loss have not been completely clarified. The diminished osteoblast function is accompanied by a comparable or even greater increase in osteoclast activity. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway has been recently recognized as the final, dominant mediator of osteoclast proliferation and activation. There is increased evidence that this pathway interferes in the pathogenesis of thalassaemia-induced osteoporosis. Currently, bisphosphonates that are potent inhibitors of osteoclast function have been used in TM patients with encouraging results. This review attempts to summarize all the novel data for the biology of bone damage in TM. It also describes the results of all major studies that have investigated the effects of different treatment modalities for TM-induced osteoporosis, their mode of action, and the future implications of their use.
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PMID:New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia. 1546 18

Osteopathy, as a major feature of homozygous beta-thalassaemia, is a multifactorial disorder, not fully understood. We studied the lumbar vertebrae of 48 patients using Dual-Energy X-ray Absorptiometry (DXA) and Quantitative Computed Tomography (QCT), and we focused on structural properties, assessed by High Resolution Computed Tomography (HRCT). Bone Mineral Density (BMD) values were expressed as Z-scores and the results were correlated. The effect of age, sex, and type of thalassaemia and hormonal factors on BMD was assessed. We estimated, with HRCT, the cortex integrity and the number and thickness of trabeculae; the latter were classified to a three-grade scale. Our results showed the overall prevalence of osteoporosis to be 44% with DXA and 6% with QCT. Both techniques revealed an inverse correlation between age and BMD, whereas hormonal factors demonstrated associations with QCT and DXA measurements. The correlation coefficient between DXA's BMD and QCT's trabecular BMD was 0.545 (P < 0.001) whereas the corresponding value for Z-scores was r = 0.491 (P < 0.001). The classification of the patients into normal, osteopenic and osteoporotic categories, using QCT's Z, was in better agreement with the assignment based on trabecular number (K = 0.209, P = 0.053) than the classification using DXA's Z (K = 0.145, P = 0.120). Cortex evaluation by HRCT showed discontinuity in 15 patients. Both methods indicate a progression of osteoporosis with age. Hormonal deficiency is associated with thalassaemic osteoporosis whereas the visual estimation of cortex indicates that Thalassaemia Intermedia (TI) patients could be more affected than Thalassaemia Major (TM). Using the trabecular number as an indicator of osteoporosis, it seems that QCT may evaluate osteopathy better than DXA. Since the former has the ability to measure trabecular and cortical BMD separately, it could give early indication of which changes more rapidly and to what degree.
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PMID:Comparison of DXA, QCT and trabecular structure in beta-thalassaemia. 1581 18

Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450; P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients.
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PMID:Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation. 1596 88

The prospects of using chelating agents for increasing the excretion of actinides are reviewed. The removal of plutonium by chelating agents is of great importance because plutonium is extremely dangerous and induces cancer due to radiation toxicity. Similarly, uranium is a radionuclide, which causes severe renal dysfunction within a short time period due to chemical toxicity. It may also induce cancers such as leukemia and osteosarcoma in cases of long-term internal radiation exposure. Investigations on chelating agents for the removal of plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic acid (DTPA) is recognized as a chelating agent that accelerates the excretion of plutonium in early treatment after an accident. Thereafter, there has long been an interest in finding new chelating agents with radionuclide removal properties for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA have been studied for their ability to remove plutonium and uranium. Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within this context, it is important to examine the clinical use of these two drugs as well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in order to identify possible uses in the treatment of radiation workers contaminated with plutonium and uranium.
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PMID:Chelating agents used for plutonium and uranium removal in radiation emergency medicine. 1630 71

The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.
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PMID:Survival and complications in thalassemia. 1633 50


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