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 commonly occurring short stature in the condition of thalassaemia major was investigated with respect to the possible role of the somatomedin growth factor low molecular weight non-suppressible insulin-like activity (NSILAs). Nineteen affected patients (12 boys, 7 girls) aged between 2 and 21 years were studied. Twelve of them were on or below the 10th centile for height of whom 7 were on or below the 3rd centile for height. Serum immunoreactive growth hormone responses to exercise were normal in 9 of 11 subjects tested. Using an isolated fat cell bioassay NSILAs was undetectable in 10 and was more than 2 SD below the normal mean value in the other 9 subjects. High molecular weight NSILA (not a growth factor) was very low or undetectable in all 9 subjects tested. Low molecular weight NSILAs did not show the normal correlation with age in childhood, nor was there any correlation with height, height velocity, or bone age. The 2 children above the 50th centile for height had undetectable NSILAs. There was no evidence of iron or ferritin interfering in the bioassay, and mixing experiments showed no evidence of inhibitory activity towards NSILAs in thalassaemic sera. Low circulating levels of the somatomedin NSILAs may contribute to the short stature in thalassaemia major, but other factors may permit normal growth in some affected children.
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PMID:Deficiency of non-suppressible insulin-like activity in thalassaemia major. 730 29

We have found bioassayable somatomedin activity to be subnormal in 20 of 32 children and adults with beta-thalassemia. The levels were comparable to values reported in growth hormone-deficient subjects. Since patients with thalassemia are not growth hormone deficient, the data suggest the possibility of defective hepatic biosynthesis of somatomedin. Increased iron stores in these patients, who have secondary hemosiderosis of many organs, including the liver, may depress somatomedin activity. Therapy for one year with daily subcutaneous infusions of the iron-chelating agent deferoxamine had no effect on mean bioassayable serum somatomedin activity.
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PMID:Depressed serum somatomedin activity in beta-thalassemia. 735 82

Patients with beta-thalassaemia (major, minor, and in association with sickle cell gene) frequently suffer from growth retardation and delayed sexual development. This is believed to be due, at least in part, to a direct effect of iron overload on the endocrine mechanisms of puberty. The role of iron overload remains speculative in relation to the disease severity and ethnic variations. This study determined the level of testosterone, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), free thyroxine (T4), tri-iodothyronine (T3), growth hormone (GH), iron, ferritin, and haematological parameters in 44 beta-thalassaemia patients (21 = beta-thal. major, 23 beta-thal minor), 25 Hb S/beta zero-thalassaemia patients, and 50 normal controls with age range 2-15 years. The iron endocrine status and haematological findings were evaluated, and the results were correlated and compared with age- and sex-matched controls. In comparison with controls the beta-thalassaemia-major and the Hb S/beta zero-thalassaemia patients had a significantly higher level of plasma ferritin (P < 0.01) while the mean level of total haemoglobin was significantly lower. The level of LH, FSH, testosterone, and plasma cortisol were lower in both beta-thalassaemia-major and Hb S/beta zero-thalassaemia patients with a negative correlation with plasma ferritin level. Free T3 and T4 were raised, but the difference was not statistically significant. The data demonstrate the occurrence of impaired endocrine function in the beta-thalassaemia and Hb S/beta zero-thalassaemia patients.
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PMID:Iron-endocrine pattern in patients with beta-thalassaemia. 793 35

Disturbances of growth and development in patients with thalassaemia receiving hypertransfusion programmes are well recognised and are most likely to be due to iron overload. The extent of endocrine dysfunction was investigated in a group of 18 patients thought to have been treated by acceptable modern standards, 11 of whom could be considered as well chelated. Assessment of growth and puberty showed a wide variation in height SD scores with five patients having significantly short stature. Most patients are progressing through puberty normally with the exception of two boys with marked pubertal delay. The most prominent finding was that growth hormone responses to glucagon stimulation were significantly impaired in all of the patients with iron overload. Basal endocrine assessment showed primary hypothyroidism in two patients aged 16.8 and 12.9 years with plasma thyroxine-concentrations of 86 and 59 nmol/l (normal range 65-165 nmol/l) and plasma thyroid stimulating hormone 10.2 and 30.3 mU/l (normal range 0.5-5 mU/l). One patient had diabetes mellitus. These results show that even when ideal management is sought a significant amount of endocrine damage occurs; surveillance of these patients is thus essential.
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PMID:Relationship of endocrinopathy to iron chelation status in young patients with thalassaemia major. 794 32

Recombinant human growth hormone (rhGH) is now available for treatment of short stature due to growth hormone (GH) deficiency. It's potential use in other causes of short stature raises concerns about adverse effects of long term treatment on carbohydrate and lipoprotein metabolism. We describe the serial changes in lipids, lipoproteins and apolipoproteins, including apo(a) in 12 children with beta-thalassaemia major undergoing rhGH treatment for 24-36 months. All showed satisfactory increases in height and weight. A significantly higher mean plasma apo(a) was observed at 3 months (102.6 U/l) versus baseline (71.4 U/l, P < 0.01, geometric means). Subsequently apo(a) levels gradually decreased returning to pretreatment levels after 36 months of rhGH treatment. There were parallel rises and falls in the apo(a) isoforms of different sizes during treatment. There were only minimal changes in the other lipid related parameters. All children had markedly reduced cholesterol levels (3.0 +/- 0.49 mmol/l, mean +/- S.D.) characteristic of their underlying disease. In conclusion the elevation of apo(a) by GH is only transient, there is no differential effect of rhGH on the large and small isoforms of apo(a) and there are no clinically significant adverse effects of rhGH treatment on lipoprotein metabolism.
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PMID:Growth hormone therapy transiently increases apolipoprotein(a) in short beta-thalassaemia major children with normal growth hormone reserve. 905 Jul 74

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.
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PMID:Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. 959 44

Growth failure is commonly described in polytransfused thalassaemia major patients (Th) with or without growth hormone (GH) releasing hormone-GH axis impairment. We have investigated the efficacy of short-term recombinant GH (rhGH) therapy (Saizen [Serono] 0.1 IU/kg/day 6 evenings/week administered s.c. for 12 months) on growth and predicted final height in 28 (19M, 9F) regularly transfused Th with growth deficiency (aged 14.8 +/- 2.0 yr) on long term desferrioxamine s.c. therapy. All Th had no evidence of congestive heart failure, hypothyroidism or impaired glucose tolerance; in all patients the GH peak (evaluated during both insulin and clonidine test) was < or = 20 mIU/l; hypergonadotropic hypogonadism was excluded in Th with delayed puberty. At the start of therapy height age (HA)/bone age (BA) ratio was 0.92 +/- 0.12. Bone age delay was positively correlated to chronological age (CA), serum ferritin levels (mean of the last three years), the age at the start of chelation therapy, growth velocity calculated for CA during the last year; a positive correlation was also found between circulating IGF-I levels and age at the start of chelation therapy. After 1 year on rhGH therapy there was a significant increase of height calculated for CA (not for BA), of growth velocity calculated for both CA and BA and of circulating IGF-I levels; the HA variation/BA variation ratio was 1.85 +/- 1.71, without any significant difference between predicted final height at the start (-1.08 +/- 1.28 SDS) and at the end of rhGH therapy (-0.88 +/- 1.13). The variation of height calculated for CA was positively correlated to both CA and growth velocity during the last year before rhGH therapy (calculated for CA) and negatively to the height at the start (calculated for CA). There were no side effects and haematological parameters did not show significant changes. In conclusion, our data, obtained in a relatively large group of Th, confirm the emerging results of short-term (12 months) rhGH therapy on growth, as shown by the increase of both growth velocity and height calculated for CA. With regard to final height, although the mean variation of HA/variation of BA ratio was 1.85, no significant increase of the predicted final height was found between the start and the end of rhGH therapy. We are evaluating the effect of long-term rhGH therapy on growth in these patients.
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PMID:Short-term therapy with recombinant growth hormone in polytransfused thalassaemia major patients with growth deficiency. 1009 Nov 55

The acute response to various doses of human growth hormone (hGH) was determined in short patients with thalassaemia and compared to that in patients with classic growth hormone deficiency and Turner's syndrome. Nitrogen balance was analyzed using the stable isotope 15N. While patients with growth hormone deficiency responded with a marked nitrogen retention (+2.9 +/- 0.4 to +6.1 +/- 0.6 mg 15N/kg) to small doses of hGH (2 x 3 IU/m2), those with Turner's syndrome had a higher basal balance, but responded much less (+3.1 +/- 0.7 to +3.7 +/- 1.8 mg 15N/kg). They required a double dose of hGH (2 x 6 IU/m2) to achieve a significant retention (+4.1 +/- 1.0 to +7.1 +/- 0.4 mg 15N/kg). The thalassaemic patients responded still less than the patients with Turner's syndrome to 2 x 6 IU/m2 (+7.7 +/- 0.3 to +8.0 +/- 0.4 mg 15N/kg), and even hGH doses up to 2 x 12 IU/m2 had little effect, indicating a relative resistance to hGH. In conclusion, no or little effect is to be expected from long-term hGH treatment at low doses in thalassaemic patients. When it is decided to treat these patients, the dose should be about 4 times higher than a regular replacement dose in growth hormone deficiency.
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PMID:Acute metabolic effects of human growth hormone on 15N-nitrogen balance in patients with thalassaemia as compared to patients with other types of short stature. 1009 Nov 56

Short tandem repeats are abundantly present within the genome. They are commonly used as polymorphic markers but their potential functional role is poorly documented. Several of these microsatellites have been described within the beta-globin locus and some could be involved in controlling gene expression. Our purpose was to investigate the extent and significance of the (TG)n(CG)m dinucleotide repeat polymorphisms in the two gamma-globin gene IVS2s. Two groups of subjects were studied: a group of 63 beta-thalassaemic patients presenting either with a severe Cooley's anaemia (n=50) or with thalassaemia intermedia (TI, n=13), and a control group of 60 unrelated healthy individuals. A high heterogeneity of the polymorphic repeats was demonstrated, extending the range of the published alleles from 13 to 22 and allowing a first attempt at making a phenotype/genotype correlation. One specific allele, (TG)13 in the Agamma-gene, was highly enriched in the TI patients (46.1% vs 2.9% of the Cooley's anaemia cases, P < 0.0002, and 23.3% in the normal controls, P < 0.008) and preferentially observed in TI patients with a high haemoglobin F (Hb F). Transient transfection assays in K562 cells, with the growth hormone gene as a reporter, showed a positive regulatory action mediated by a (TG)13-containing 243 nt IVS2 fragment. Finally, a first set of mobility shift experiments with erythroid (K562 and MEL) and nonerythroid (HeLa) cell lines showed binding of erythroid component(s) in this DNA region and the binding pattern was modified upon induction of MEL cells by DMSO. Thus, our in vivo and in vitro data raise the question of a possible contribution of the gamma-gene IVS2s polymorphic microsatellites to the variable Hb F synthesis in the major haemoglobinopathies: a well known, puzzling and still unanswered question.
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PMID:Genetic variations in human fetal globin gene microsatellites and their functional relevance. 1036 60

Children with chronic illness live with the specific consequences of their illness, as well as secondary endocrine abnormalities that further compromise growth and pubertal development. These secondary abnormalities may significantly add to their physiologic and psychological burden. Although these endocrine abnormalities theoretically arise as adaptations to the chronic illness, they may have deleterious effects if they persist untreated. Children with HIV infection and other wasting disorders, for example, show growth suppression out of proportion to the severity of their primary illness as a result of growth hormone resistance and enhanced cortisol secretion. In hematologic conditions such as sickle cell anemia, thalassemia, or bone marrow transplant, damage to the hypothalamus and/or pituitary may lead to growth hormone deficiency, gonadal insufficiency, and hypothyroidism. Growth and pubertal delay are also common among children with cystic fibrosis, along with insulin-dependent diabetes mellitus caused by pancreatic fibrosis. Similarly, children receiving long-term steroid therapy have delays in growth and pubertal development, accompanied by risk for osteoporosis, whereas chronic renal disease is associated with growth and pubertal delay, as well as secondary hyperparathyroidism. Recognition of potential endocrinopathies in children with chronic illness is an important aspect of the care of these children because the disturbances are frequently amenable to treatment, permitting full or partial restoration of normal growth and development in these children. In this chapter, the endocrine consequences of common chronic conditions of childhood are reviewed, as well as the etiology of the endocrine disturbance, the clinical consequences, and recommendations for treatment.
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PMID:Advances in the recognition and treatment of endocrine complications in children with chronic illness. 1064 63


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