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)

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.
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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.
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PMID:Serum 1,25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major. 349 58

Calcium and phosphorus disturbances in childhood are discussed in vitamin D deficiency rickets, neonatal tetany and beta-homozygous thalassaemia. The nutritional, epidemiological, hereditary and other factors facilitating the development of the disease in these three groups of children are illustrated. The level of culture and sociability of the community must be taken into consideration for the success of the preventive medicine services, especially with regard to vitamin D deficiency rickets. The administration of phosphorus and vitamin D or metabolites of vitamin D to thalassaemic children would probably produce beneficial effects on bone and muscle changes.
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PMID:Calcium and phosphorus disturbances in children. 708 72

Bone disease is an important cause of morbidity in older patients with beta-thalassaemia major and intermedia. We studied 27 women and 23 men with beta-thalassaemia major (37) and intermedia (13) whose mean age was 32.3 +/- 9.7 years. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius was determined by dual-energy X-ray absorbiometry (DXA). The longitudinal change in BMD over a mean of 5.6 years was determined in 19 patients. Serum 25-hydroxyvitamin D, insulin growth factor-1 (IGF-1), bone formation markers bone-alkaline phosphatase, osteocalcin and the resorption marker urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined. The BsmI vitamin D receptor (VDR) gene polymorphism was analysed. Reduced BMD (Z-score < -2) was present in 89%, 62% and 73% of patients in the spine, hip and radius respectively. Vitamin D deficiency was found in 62%, decreased IGF-1 in 72% and increased urinary NTx in 84% of patients. Serum IGF-1 correlated with spine and hip BMD (r = 0.4, r = 0.39, P < 0.01 respectively), and NTx correlated with the hip BMD Z-score (r = 0.35 P < 0.05). The mean annual percentage change in spine BMD was -1.36%. Patients with the VDR BB genotype had lower spine BMD than patients with the bb genotype. In conclusion, bone loss continues in adult thalassaemia patients and is associated with increased bone resorption and decreased IGF-1. The BsmI VDR gene polymorphism is associated with osteopenia in thalassaemia.
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PMID:Bone mineral metabolism in adults with beta-thalassaemia major and intermedia. 1112 54

The population of Quebec, Canada (7.3 million) contains approximately 6 million French Canadians; they are the descendants of approximately 8500 permanent French settlers who colonized Nouvelle France between 1608 and 1759. Their well-documented settlements, internal migrations, and natural increase over four centuries in relative isolation (geographic, linguistic, etc.) contain important evidence of social transmission of demographic behavior that contributed to effective family size and population structure. This history is reflected in at least 22 Mendelian diseases, occurring at unusually high prevalence in its subpopulations. Immigration of non-French persons during the past 250 years has given the Quebec population further inhomogeneity, which is apparent in allelic diversity at various loci. The histories of Quebec's subpopulations are, to a great extent, the histories of their alleles. Rare pathogenic alleles with high penetrance and associated haplotypes at 10 loci (CFTR, FAH, HBB, HEXA, LDLR, LPL, PAH, PABP2, PDDR, and SACS) are expressed in probands with cystic fibrosis, tyrosinemia, beta-thalassemia, Tay-Sachs, familial hypercholesterolemia, hyperchylomicronemia, PKU, oculopharyngeal muscular dystrophy, pseudo vitamin D deficiency rickets, and spastic ataxia of Charlevoix-Saguenay, respectively) reveal the interpopulation and intrapopulation genetic diversity of Quebec. Inbreeding does not explain the clustering and prevalence of these genetic diseases; genealogical reconstructions buttressed by molecular evidence point to founder effects and genetic drift in multiple instances. Genealogical estimates of historical meioses and analysis of linkage disequilibrium show that sectors of this young population are suitable for linkage disequilibrium mapping of rare alleles. How the population benefits from what is being learned about its structure and how its uniqueness could facilitate construction of a genomic map of linkage disequilibrium are discussed.
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PMID:Human genetics: lessons from Quebec populations. 1170 44

Adult thalassemic patients have reduced bone mass due to disturbances in several different mechanisms affecting bone turnover. To determine if vitamin D deficiency contributes to the low bone mass of adult thalassemic subjects, we studied serum 25-OH-vitamin D levels in 90 patients (age ranging between 21 and 48 years) affected with thalassemia major (TM) and 35 (age 21-56 years) with thalassemia intermedia (TI). TM patients had been receiving regular transfusions from the age of 2 years and had increased serum ferritin, glutamic oxalacetic transaminase, glutamic piruvic transaminase as well as low bone density (L1-L4 Z score -2.07 +/- 0.2). TI patients did not receive transfusions, but their ferritin levels were increased as well (520.3 +/- 138,1). 8 TM patients (10.1%) and 4 TI (11.4%) had serum 25-OH-vitamin D less than 10.4 ng/ml and were considered presenting an absolute deficiency of vitamin D. Mean 25-OH-vitamin D was significantly (P < 0.01) lower in both TM and TI patients (20.3 +/- 0.7 ng/ml and 20.9 +/- 2.3 ng/ml, respectively) than in 100 healthy control subjects of similar age (25.2 +/- 1 ng/ml). 1,25-OH-vitamin D levels were in the normal-lower levels (45.15 +/- 1.5 mg/dl), while 24 H urinary calcium was below the normal range (15.75 mg/dl). In TM patients, the 25-OH-vitamin D levels correlated negatively with age (P < 0.05) and with serum ferritin (P < 0.05). TM and TI patients with low 25-OH-vitamin D levels (<17.8 ng/ml) presented higher serum ferritin levels (P < 0.01) and higher PTH (P < 0.05) compared to those with normal vitamin D. Moreover, TM patients with low 25-OH-vitamin D levels were significantly older (P < 0.05) and had higher GPT (P < 0.05) than patients with normal vitamin D. In conclusion, calcium metabolism is frequently impaired in adult thalassemic patients. An early and effective medical treatment should be taken in consideration by the clinician in order to improve the bone health in these patients.
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PMID:Low serum levels of 25-hydroxy vitamin D in adults affected by thalassemia major or intermedia. 1646 53

Vitamin D25-OH and D1-25OH levels were compared with cardiac R2* (1/T2*), left ventricular ejection fraction (LVEF), age, ferritin and liver iron in 24 thalassaemia major patients. Vitamin D25-OH levels were reduced in 13/24 patients while vitamin D1-25OH levels were often elevated. Vitamin D25-OH levels decreased with age (r(2) = 0.48) and with liver iron (r(2) = 0.20). Cardiac R2* was inversely related with the ratio of D25-OH to D1-25OH levels (r(2) = 0.42). LVEF was also proportional to the D25-OH/D1-25OH ratio (r(2) = 0.49). Vitamin D deficiency may be associated with cardiac iron uptake and ventricular dysfunction in thalassaemia major patients.
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PMID:Vitamin D deficiency, cardiac iron and cardiac function in thalassaemia major. 1837 Nov 8

The primary cause of cardiac dysfunction in thalassemia is believed to be myocardial iron overload. Besides iron, other factors may play a role in the impairment of myocardial contractility, including prolonged heart tissue hypoxia, pericardial involvement, arrhythmias, endocrine complications and vitamin D deficiency. We present the case of a 7 year-old boy with ?-thalassaemia major and cardiac dysfunction, pericardial effusion and associated endocrinopathies. His serum thyrotropin (TSH) level was increased, and total and free thyroxine (FT4) were low. In addition, biochemical results and serum PTH level were compatible with a diagnosis of hypoparathyroidism. Other laboratory findings were not consistent with rheumatic heart disease, viral myocarditis or autoimmune disease. The child was treated with digoxin, diuretics, oral calcium, vitamin D, L-thyroxine (25 microg daily, which was later gradually increased) and subcutaneous iron chelation therapy (45 mg/kg, six days/week). The patient was discharged from our Unit after 7 days and within 3 months he had appreciable myocardial improvement and disappearance of the pericardial effusion.
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PMID:Cardiomyopathy and pericardial effusion in a 7 year-old boy with beta-thalassaemia major, severe primary hypothyroidism and hypoparathyroidism due to iron overload. 1933 75

Osteoporosis in thalassaemia major (TM) represents a prominent cause of morbidity. The mechanism of pathogenesis of bone disease (BD) in TM is multifactorial and complicated. Peak bone mass is achieved shortly after completion of puberty and normally remains stable until the third decade of life when age-related bone mass begins. Growth hormone (GH) and sex steroids play a crucial role in bone remodeling and in the maintenance of skeletal architecture during adult life. GH and insulin growth factors (IGFs) have anabolic effect in bone formation. Sex steroids act probably by increasing the expression of RANKL by osteoblastic cells and alterations in the RANK/RANKL/OPG system in favor of osteoclasts. Impaired GH secretion and lack of sex steroids in thalassemic patients due to pituitary damage, contribute to failure of achieving optimal peak bone mass. Other endocrine complications such as hypoparathyroidism and vitamin D deficiency have also a detrimental role on bones in TM. It is still questionable whether the international criteria for defining osteopenia and osteoporosis are relevant to patients with TM; also a question arises for the diagnostic methods such as DEXA scan and management of osteoporosis with known treatment protocols, in the thalassaemic patient.
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PMID:Osteoporosis syndrome in thalassaemia major: an overview. 2097 89

Bone is a dynamic organ, constantly changing metabolically and being remodelled through the balanced activity of osteoclast and osteoblast on trabecular surfaces. Osteoporosis represents a continuum, in which multiple pathogenic mechanisms converge to cause loss of bone mass and deterioration of microarchitecture of skeletal structure. In thalassaemia major (TM), progressive 'aging' of bone starts in early childhood, through the gradual development of an imbalance between augmented osteoclastic resorption and insufficient osteoblastic bone formation. Chronic anemia, iron toxicity and endocrine complications, via a complex mechanism, lead to alterations in the RANK/RANKL/OPG system in favor of increased osteoclastic activity and enhanced osteoblastic dysfunction. Hypogonadotrophic hypogonadism and delayed puberty are the most common endocrine complications in patients with TM; they also contribute to osteopenia and osteoporosis, which is present in more than 50% of patients. There are gender differences not only in the prevalence but also in the severity of the osteoporosis syndrome. The anabolic effects of GH and IGF-1 on bone formation are important for the acquisition of bone mass, mainly during childhood and puberty. In TM, GH secretory dysfunction is common and contributes to osteopenia and osteoporosis, along with other endocrinopathies such as hypoparathyroidism and vitamin D deficiency, hypothyroidism and diabetes. Prevention is with no doubt the first step in the management of osteoporosis in TM, with the final goal of preventing bone loss and fractures. The management of patients with TM should start as early as birth in order to minimize the disease complications. Induction of puberty at a proper age with estrogens in girls and testosterone in boys and later treatment of hypogonadism with HRT are vital steps in the prevention of bone disease in TM. Biphosphonates, the well known medication for osteoporosis, have been tried in the treatment of TM-osteoporosis with promising outcomes. Since the origin of bone disease in TM is multifactorial and some of the underlying pathogenic mechanisms are still unclear, further research in this field is needed, which will allow the design of optimal therapeutic measures.
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PMID:Bone disease in thalassaemia major: recent advances in pathogenesis and clinical aspects. 2170 82


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