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)

Since the discovery of HFE gene in 1996, considerable progress has been made concerning the iron-metabolism and its major abnormalities. Five types of hereditary hemochromatosis are actually known: type 1 (HFE gene), type 2A (HJV gene), type 2B (HAMP gene), type 3 (TfR2 gene), type 4 (SLC40A1 gene). The HFE C282Y +/+ mutation is responsible for the most frequent type of hemochromatosis in France. Various secondary causes can lead to iron-overload: associated genetic diseases, exogenous iron intake, thalassaemia and refractory anaemia, hepatic siderosis, alcoholic hepatitis, cutaneous porphyria and cirrhosis. The deleterious consequences of iron-overload are due to the interactions of the environmental factors. The role of HFE heterozygote mutations is still discussed. In clinical practice, the interpretation of a serum ferritin increase is a frequent problem that needs a careful evaluation based on the tranferrin saturation measurement. Significant increase of both these factors is in favour of an HFE C282Y +/+ hemochromatosis, after exclusion of a hepatocellular insufficiency or a refractory anaemia. Nevertheless, high ferritin is not always a marker of iron-overload. Thus, there are many disorders increasing the serum ferritin levels without iron overload : cytolysis (hepatic...), inflammatory or infectious syndromes, high alcohol intake, neoplasia... Looking for HFE mutations help to separate type 1 hemochromatosis from other conditions mainly hepatic siderosis (metabolic disorders). The identification of rare types of hemochromatosis (types 2-4) is only required in particular cases. The evaluation of the iron overload is now based on hepatic MRI determination rather than liver biopsy. Repeated phlebotomies remain the essential way to decrease the iron overload in HFE hemochromatosis and to prevent the occurrence of severe and irreversible complications (cirrhosis, arthropathies, cardiac failure, and diabetes). Because of the link established between the amount of iron-overload and the occurrence of complications and the mortality over-risk in HFE C282Y +/+ hemochromatosis, venesections must be started when serum ferritin is higher than 300 microg/l in man and 200 microg/l in woman, whatever the clinical manifestations are and obviously before the symptomatic phase of the disease.
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PMID:[Hereditary and acquired iron overload]. 1737 75

Hemolytic anemias can induce various anomalies of the endocrine glands which can already be observed in children. Endocrine dysfunction is also found in the course of therapy for aplastic anemias, usually as undesirable side effects. In Europe, 2-9% of the population belongs to ethnic minorities at risk for developing hemolytic anemia. Pituitary affinity to iron deposition explains the high incidence of hypogonadism, puberty delay and growth retardation although other factors have to be considered. Growth hormone deficiency has to be ruled out as it can occur in a minority of subjects with thalassemia and sickle-cell disease (drepanocytosis). Diabetes mellitus, hypothyroidism and hypoparathyroidism may also develop. Follow-up includes close monitoring of growth and pubertal development in order to guide therapeutic interventions.
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PMID:[Severe chronic anemia and endocrine disorders in children]. 1752 72

Chronic hypercoagulable state expressed clinically by thromboembolic events has been described in thalassemia. One of the affected organs is the brain where symptomatic and asymptomatic damage has been reported. The present report describes seven cases who presented with the signs of cerebrovascular accident (CVA), five ischemic and two with hemorrhage. Two of them died. All patients were splenectomized, five received regular blood transfusions, and their ferritin levels were between 1,200 and 3,000 mg %. In addition, four patients had congestive heart failure and atrial fibrillation, and three had "Bronze diabetes," The recommendation on the basis of the results is that well-designed clinical trials are indicated to monitor asymptomatic brain damage by magnetic resonance imaging in splenectomized patients over the age of 20 years, who are not regularly transfused and have a high risk to develop thromboembolic events. In this subset of patients, anticoagulant and/or antiplatelet therapy should be considered. Moreover, treatment of additional complications resulting from iron overload, which may contribute to the etiology of CVA such as cardiac failure and arrhythmia with or without "bronze diabetes," is mandatory.
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PMID:Cerebrovascular accident in beta-thalassemia major (beta-TM) and beta-thalassemia intermedia (beta-TI). 1818 11

Patients with multi-transfused thalassaemia major may develop severe endocrine complications due to iron overload. The anterior pituitary is particularly sensitive to iron overload which disrupts hormonal secretion resulting in hypogonadism, short stature , acquired hypothyroidism and hypoparathyroidism. Glucose intolerance and diabetes mellitus are also common in thalassaemic patients. The severity of the clinical manifestation and laboratory findings in thalassaemia largely depends on the genotype; thus homozygotes or compound heterozygotes for the mutations beta0 or beta+ depend for life on frequent transfusions. A multicenter study in Cyprus including 435 patients showed hypogonadotrophic hypogonadism in 32.5%, short stature in 35%, acquired hypothyroidism in 5.9%, hypoparathyroidism in 1.2% and diabetes mellitus in 9.4%. A slowing down of growth velocity and a reduced or absent pubertal growth spurt is observed in early adolescence leading to short adult height. Delayed or absent puberty and hypogonadism may result in fertility problems which affect enormously the life of thalassemics. Glucose intolerance in adolescence and diabetes mellitus later in life are also frequent complications mainly due to iron overload, chronic liver disease and genetic predisposition. Primary hypothyroidism and hypoparathyroidsm usually appear in the second decade of life; are related to iron overload and may be reversible at an early stage by intensive chelation. Osteopenia and osteoporosis due to a complicated pathogenesis represent prominent causes of morbidity in young adults of both genders with thalassaemia. Early recognition and prevention of the endocrine complications, by early and regular chelation therapy, is mandatory for the improvement of the quality of life and psychological outcome of these patients.
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PMID:Endocrine complications in patients with Thalassaemia Major. 1808 58

Recent developments in the understanding of the molecular control of iron homeostasis provided novel insights into the mechanisms responsible for normal iron balance. However in chronic anemias associated with iron overload, such mechanisms are no longer sufficient to offer protection from iron toxicity, and iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic damage. Today, long-term deferoxamine (DFO) therapy is an integral part of the management of thalassemia and other transfusion-dependent anemias, with a major impact on well-being and survival. However, the high cost and rigorous requirements of DFO therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Within recent years more than one thousand candidate compounds have been screened in animal models. The most outstanding of these compounds include deferiprone (L1); pyridoxal isonicotinoyl hydrazone (PIH) and; bishydroxy- phenyl thiazole. Deferiprone has been used extensively as a substitute for DFO in clinical trials involving hundreds of patients. However, L1 treatment alone fails to achieve a negative iron balance in a substantial proportion of subjects. Deferiprone is less effective than DFO and its potential hepatotoxicity is an issue of current controversy. A new orally effective iron chelator should not necessarily be regarded as one displacing the presently accepted and highly effective parenteral drug DFO. Rather, it could be employed to extend the scope of iron chelating strategies in a manner analogous with the combined use of medications in the management of other conditions such as hypertension or diabetes. Coadministration or alternating use of DFO and a suitable oral chelator may allow a decrease in dosage of both drugs and improve compliance by decreasing the demand on tedious parenteral drug administration. Combined use of DFO and L1 has already been shown to result in successful depletion of iron stores in patients previously failing to respond to single drug therapy, and to lead to improved compliance with treatment. It may also result in a "shuttle effect" between weak intracellular chelators and powerful extracellular chelators or exploit the entero-hepatic cycle to promote fecal iron excretion. All of these innovative ways of chelator usage are now awaiting evaluation in experimental models and in the clinical setting.
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PMID:Objectives and methods of iron chelation therapy. 1836 50

Thalassemia is common in Iran. Appropriate therapy for this disease includes a regular blood transfusion and chelation therapy. However, in this approach patients will inevitably experience side effects, particularly iron overloads in critical organs, including heart, ductless glands, and liver. This study attempted to determine prevalence of adenoidal abnormality between Iranian thalassemia patients for prediagnosis and to offer necessary medical measures. This is a descriptive nonrandomized study and included all the patients suffering from thalassemia major referring to medical centers linked with the Iranian blood transfusion organization from January 2004 to January 2005. All patients were sampled for CBC, FBS, 2-h BS, HbAlC, liver function, renal function, and endocrine disease. Initially, reports of adenoidal experiments as well as other associated parameters were provided from medical records. A total of 437 patients enrolled in the study: 5.4% suffered from diabetes, 1% had hypothyroid, and 1 person showed hypoparathyroidism. The mean levels of ferritin in diabetic and nondiabetic groups and hypothyroid and nonhypothyroid groups were not significantly different. The mean levels of ferritin among various age groups also were not significantly different. Results of a comparison between present research and similar studies conducted throughout Iran and those performed abroad on adenoidal abnormalities in thalassemia patients show that subject patients of this study statistically suffered from fewer difficulties than diabetes patients in other studies.
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PMID:Endocrinopathies in patients with transfusion-dependent beta-thalassemia. 1843 1

Chronic leg ulcers affect about 1% of the German population. The intense search for the underlying cause of impaired wound healing is an essential requirement for successful therapy. The most common causes comprise chronic venous insufficiency (70%), peripheral arterial occlusive disease (10%) and diabetes mellitus. Besides vasculitis, infectious diseases and tumors, genetic diseases may constitute the underlying cause for impaired wound healing. In this review various rare genetic diseases causing chronic wounds like the Klinefelter-Syndrome, immunological diseases including the TAP-deficiency-syndrome and the leukocyte adhesion deficiency-syndromes, red blood cell disorders, thalassemia, thrombotic diseases, progeroid syndromes and inherited connective tissue disorders are presented.
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PMID:[Genetic causes of impaired wound healing. Rare differential diagnosis of the non-healing wound]. 1893 1

Frequent blood transfusions can lead to iron overload which may result in several endocrine complications especially in the absence of adequate chelation therapy. The objectives of this study are to determine the prevalence of endocrine complications in transfusion dependent thalassaemia patients and the correlation of endocrine complications with the degree of iron chelation. This retrospective study looked at cases of adult patients with transfusion dependent thalassaemia treated in the Haematology Unit, Penang Hospital. Of the 25 transfusion dependent thalassaemia patients, there were 10 male and 15 female patients respectively with almost equal number of Malay and Chinese patients (13 and 12 patients respectively). Short stature was seen in 36.0% of our patients. In our cohort, 12 patients had delayed puberty (male 70.0% and female 33.3%). Prevalence of osteoporosis was 36.0%. Hypogonadism was noted in 40.0% of males and 46.7% of females. 53.4% of the female population had menstrual abnormalities with prevalence of primary and secondary amenorrhoea at 26.7% each. The prevalence of other endocrinopathies was much lower: 8.0% had diabetes mellitus and only one patient had hypocortisolism. Iron chelation appeared insufficient in our study population. The high frequency of endocrine complications noted in our study supports the rationale for regular follow-up of transfusion dependent thalassaemic patients to ensure early detection and timely treatment of associated complications.
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PMID:Endocrine complications in transfusion dependent thalassaemia in Penang Hospital. 1894 94

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, has a wide range of clinical manifestations. Here, we describe rheumatological melioidosis (involving one or more of joint, bone or muscle), and compare features and outcome with patients without rheumatological involvement. A retrospective study of patients with culture-confirmed melioidosis admitted to Sappasithiprasong Hospital, Ubon Ratchathani during 2002 and 2005 identified 679 patients with melioidosis, of whom 98 (14.4%) had rheumatological melioidosis involving joint (n=52), bone (n = 5), or muscle (n = 12), or a combination of these (n=29). Females were over-represented in the rheumatological group, and diabetes and thalassemia were independent risk factors for rheumatological involvement (OR; 2.49 and 9.56, respectively). Patients with rheumatological involvement had a more chronic course, as reflected by a longer fever clearance time (13 vs 7 days, p = 0.06) and hospitalization (22 vs 14 days, p < 0.001), but lower mortality (28% vs 44%, p = 0.005). Patients with signs and symptoms of septic arthritis for longer than 2 weeks were more likely to have extensive infection of adjacent bone and muscle, particularly in diabetic patients. Surgical intervention was associated with a survival benefit, bur not a shortening of the course of infection.
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PMID:Rheumatological manifestations in patients with melioidosis. 1905 1

This communication explores the temporal link between the age-associated increase in body iron stores and the age-related incidence of Alzheimer's disease (AD), the most prevalent cause of senile dementia. Body iron stores that increase with age could be pivotal to AD pathogenesis and progression. Increased stored iron is associated with common medical conditions such as diabetes and vascular disease that increase risk for development of AD. Increased stored iron could also promote oxidative stress/free radical damage in vulnerable neurons, a critical early change in AD. A ferrocentric model of AD described here forms the basis of a rational, easily testable experimental therapeutic approach for AD, which if successful, would be both widely applicable and inexpensive. Clinical studies have shown that calibrated phlebotomy is an effective way to reduce stored iron safely and predictably without causing anemia. We hypothesize that reducing stored iron by calibrated phlebotomy to avoid iron deficiency will improve cerebrovascular function, slow neurodegenerative change, and improve cognitive and behavioral functions in AD. The hypothesis is eminently testable as iron reduction therapy is useful for chronic diseases associated with iron excess such as nonalcoholic steatohepatitis (NASH), atherosclerosis, hereditary hemochromatosis and thalassemia. Testing this hypothesis could provide valuable insight into the causation of AD and suggest novel preventive and treatment strategies.
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PMID:Getting the iron out: phlebotomy for Alzheimer's disease? 1919 95


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