Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised. The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed.
 ...
PMID:Hormonal changes in thalassaemia major. 100 88

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.
 ...
PMID:Bone disease in children with homozygous beta-thalassemia. 230 56

In view of the claim that low 25-hydroxyvitamin D (25-OHD) concentrations may contribute to the pathogenesis of bone disease in patients with beta thalassaemia major and iron overload, we have assessed the concentrations of 25-OHD, 1 alpha,25 dihydroxyvitamin D (1 alpha,25(OH)2D), parathyroid hormone, and osteocalcin in such patients. 25-OHD concentrations were significantly lower in patients with thalassaemia major and iron overload than in controls and in some patients were subnormal or undetectable. 1 alpha,25(OH)2D concentrations were, however, normal in all patients and were similar to those in controls. Serum parathyroid hormone and plasma calcium concentrations were also normal and not significantly different from those in controls. Although 25-OHD concentrations increased significantly between January and June, there was no change in 1 alpha,25(OH)2D concentrations. 25-OHD concentrations remained lower than control values, even in June. Parathyroid hormone concentrations fell, but not significantly, between January and June, but calcium concentrations did not alter. Osteocalcin concentrations were normal in all patients except one, who had extremely low concentrations of this protein. The concentration of osteocalcin was not related to 25-OHD or 1 alpha,25(OH)2D concentrations. Thus normal calcium homeostasis is maintained in patients with thalassaemia major despite low or low-normal 25-OHD concentrations; this is probably achieved through the maintenance of normal 1 alpha,25(OH)2D concentrations, which were indistinguishable from those in controls. Normal 1 alpha,25(OH)2D, parathyroid hormone, and osteocalcin concentrations argue against an important role for vitamin D deficiency in the pathogenesis of thalassemia bone disease.
 ...
PMID:Serum 1,25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major. 349 58

Calcium and phosphate metabolism were studied in 22 patients with homozygous thalassemia. The overall results showed no significant difference for serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone, or 25-hydroxyvitamin D between thalassemic and control children. However, during the winter, serum 25-hydroxycholecalciferol levels were very significantly decreased in thalassemic children. A study of the hands showed thin metacarpal cortices related to increased resorption. Histomorphometric study of four iliac bone biopsies showed normal osteoclastic resorption and decreased bone formation. Prussian blue staining and x-ray electron microprobe analysis showed iron deposits inside the bone. Whether this finding is critical in the pathogenesis of the bone disease in unknown.
 ...
PMID:Calcium phosphate metabolism and bone disease in patients with homozygous thalassemia. 705 21

Homozygous beta-thalassemia is a severe hereditary disorder associated with osteopenia. Recently it was suggested that thalassemia minor may be a risk factor for osteoporosis. The purpose of the present study was to investigate this suggestion. Bone mineral status was assessed in 22 premenopausal women and 21 men with beta-thalassemia minor. In vivo neutron activation analysis was applied to measure hand-bone phosphorus (HBP), single-photon absorptiometry to measure forearm bone mineral content (BMC), and dual-energy X-ray absorptiometry to measure spinal bone mineral density (BMD). Comparison of the HBP, BMC, and BMD values with those of sex- and age-matched healthy subjects without the beta-thalassemia trait failed to indicate a statistically significant difference for either sex group. Concerning the biochemical markers of bone metabolism that were studied (serum calcium, phosphate, alkaline phosphatase, osteocalcin, and parathyroid hormone, and 3-h fasting urine calcium-to-urine creatinine ratio) no difference was observed between the study subjects and matched controls. In conclusion, the present study showed that subjects with beta-thalassemia minor are not at risk for osteoporosis.
 ...
PMID:Bone minerals in beta-thalassemia minor. 766 42

Serum levels of the vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D, and of osteocalcin, C-terminal parathyroid hormone and other biochemical indices related to bone metabolism, were determined in two groups of patients with beta-thalassaemia aged 5-10 years (summer 7.8 +/- 0.4 years, mean +/- SEM, and winter 7.7 +/- 0.4 years, group A, n = 15) and 11-23 years (16.6 +/- 0.9 and 15.7 +/- 0.9 years in summer and winter, respectively, group B, n = 22). Emphasis was given to populations of school and adolescent ages and to the seasons of summer and winter when vitamin D status demonstrates the widest extremes. The mean serum levels of 25-hydroxyvitamin D in patients aged 5-10 years did not differ from those of controls during both seasons studied. In contrast, in the age group 11-23 years these levels were found to be lower in patients than in controls both in winter (10.6 +/- 0.9 ng/ml vs 15.0 +/- 2.0 ng/ml, p < 0.05) and summer (20.2 +/- 2.1 ng/ml vs 27.1 +/- 2.0 ng/ml, p < 0.05). The serum concentrations of 24,25-dihydroxyvitamin D were lower in the thalassaemic patients than in controls in both age groups and both seasons. In the patients under 10 years of age the mean values of this metabolite in winter were 1.06 +/- 0.17 ng/ml vs 1.68 +/- 0.20 ng/ml in the respective controls (p < 0.05), and in summer 1.44 +/- 0.11 ng/ml vs 2.35 +/- 0.36 ng/ml in controls (p < 0.05). In the group of patients aged 11-23 years, the mean levels of 24,25-dihydroxyvitamin D were in winter 0.65 +/- 0.12 ng/ml vs 1.12 +/- 0.19 ng/ml (p < 0.05) in controls and in summer 1.34 +/- 0.12 ng/ml vs 1.84 +/- 0.20 ng/ml (p < 0.05). The 1,25-dihydroxyvitamin D concentrations in both thalassaemic patient groups were significantly no different from those in the respective control groups. Serum osteocalcin, C-terminal parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase levels in the patients studied were not significantly different from those in controls, except for calcium and phosphate in the older group. In the older group of thalassaemic patients, serum calcium was lower than in the controls (2.26 +/- 0.03 vs 2.37 +/- 0.03 mmol/l, p < 0.05) in summer and serum phosphate higher than in the controls in winter (1.47 +/- 0.05 mmol/l vs 1.27 +/- 0.06 mmol/l, p < 0.05).
 ...
PMID:Vitamin D metabolites (25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D) and osteocalcin in beta-thalassaemia. 920 93

Patients with beta-thalassemia major (beta-thalassemia) frequently have bone disorders of multifactorial etiology. We attempted to analyze the relationship between the bone mineral density ([BMD] measured by dual-photon absorptiometry) and auxanologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 (IGFBP3) axis, calcium-phosphate balance, parathyroid hormone (PTH), and cytokines (interleukin-1beta [IL-1] and tumor necrosis factor-alpha [TNF-alpha]) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature (CSS), who have normal glucose tolerance and thyroid function. Children with beta-thalassemia had a significantly decreased BMD and mean BMD% for age and sex (0.75+/-0.24 g/cm2 and 71%+/-10%, respectively) versus children with CSS (1.06+/-0.3 g/cm2 and 92%+/-7%, respectively). Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 (49+/-21 ng/mL and 1.2+/-0.25 mg/L, respectively) compared with control children (153+/-42 ng/mL and 2.1+/-0.37 mg/L, respectively). The GH response to provocation by clonidine and glucagon was defective (peak GH < 7 microg/L) in 12 of the 30 thalassemic children. Serum concentrations of IL-1beta and TNF-alpha did not differ among the two study groups. Hypocalcemia was detected in five of the 30 thalassemic patients: hypoparathyroidism was diagnosed in two of the five and rickets in the other three. BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, height standard deviation score [HSDS], and body mass index [BMI]). It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and/or GH/IGF-I therapy with supplementation with vitamin D and/or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients. Such therapy requires blinded controlled trials.
 ...
PMID:Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. 959 44

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.
 ...
PMID:Effects of thalassemia major on bone mineral density in late adolescence. 1272 13

In dialysis patients beta-thalassemia is a cause of resistance to erythropoietin (EPO). The aim of the present study is to evaluate the relationship between the amount of circulating anomalous hemoglobin chain and EPO resistance in hemodialysis. Ten hemodialyzed patients with beta-thalassemia minor were studied. The mean hemoglobin level was 9.22 +/- 0.91 g/dl, the HbA2 ranging between 5.6 and 6.8%; the weekly EPO dose was 13,500 +/- 7,185 IU/week and significantly correlated with HbA2 (r = 0.965; p = 0.0001). When stratifying patients in two groups according to HbA2 level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA2 levels, respectively, 5.7 +/- 0.1 and 6.4 +/- 0.3 g/dl, p = 0.002), it was evidenced that the need of EPO was 13,200 +/- 3,033 IU/week in LOW and 36,167 +/- 13,060 IU/week in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 +/- 4.1 IU/kg BW/week/g Hb in LOW and 21.9 +/- 10.0 in HIGH (p < 0.05). No differences were evidenced between the two groups regarding age, dialysis, body weight, serum levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum, ferritin, transferrin and parathyroid hormone. In conclusion, in patients with beta-thalassemia minor on chronic hemodialysis, the amount of anomalous hemoglobin chain directly correlate with EPO dose, strongly indicating the magnitude of resistance to erythropoietin.
 ...
PMID:Relationship between resistance to erythropoietin and high anomalous hemoglobin levels in hemodialysis patients with beta-thalassemia minor. 1458 79

Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, beta-thalassemia/hemoglobin E (beta-thal/E) with transfusion-dependency (TD) (n = 18); 2, beta-thal/E with transfusion-independency (TI) (n = 15); 3, beta-thalassemia major (beta-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the beta-major and beta-thal/E with TD groups were not significantly different. In comparison with the beta-major and beta-thal/E with TD groups, the beta-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the beta-major, beta-thal/E with TI, and HbH groups were significantly lower than those of the beta-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.
 ...
PMID:Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. 1650 22


1 2 Next >>