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)

Systemic disease, either genetic or acquired, may prevent or decrease the severity of another disease. These observations have led to important therapeutic advances. The best-known examples are Edward Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's 1942 observation that erythrocyte disorders such as thalassemia and sickle cell disease modify the severity of malaria. Patients with and carriers of cystic fibrosis may have genetic resistance to tuberculosis and/or secretory diarrhea. The beneficial effects of undernutrition have led to therapeutic diets for seizures, celiac disease, type 2 diabetes, and inflammatory bowel disease. Finasteride for prostatic hypertrophy was developed after the observation that patients with male pseudohermaphrodism resulting from 5-alpha-reductase mutations do not develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic disease prevention followed the observation that ABO incompatibility prevented Rh sensitization. The natural immunosuppression of measles may cause remission of nephrosis, and that of leprosy prevents psoriasis. Patients with one form of agammaglobulinemia (X-linked) never get Epstein-Barr virus infection, and patients with another form (common variable) are seemingly cured by HIV infection. HIV/AIDS is prevented or modified by co-receptor mutations (notably the CCRDelta32 chemokine mutation), HIV-2, or GB virus C infection. Additional exploration of these genetic, infectious, and metabolic influences on disease severity may provide new therapeutic approaches to HIV and other diseases.
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PMID:Disease versus disease: how one disease may ameliorate another. 1639 76

In contrast to genetic aberrations, epigenetic aberrations can be reversed by the use of histone acetyltransferase (HAT), histone deacetylase (HDAC), SIRT, or histone methyltransferase (HMT) inhibitors. A well-known HDACi, suberoylanilide hydroxamic acid, has been recently approved for the treatment of cutaneous T cell lymphoma, and a number of HDACi are in clinical trials as anticancer drugs. In addition, HDACi could be useful in antimalarial and antifungal therapies and can reactivate the HIV-1 expression in latent cellular reservoirs, thus suggesting the use in a combination therapy with highly active antiretroviral therapy. HDACi have also been reported to have anti-inflammatory effects through inhibition of cytokines and key transcription factors, and to ameliorate the phenotypes in animal models of neurological disorders. HDACi can also reactivate the gamma-globin gene for the treatment of beta-thalassaemia, and recently were shown to relieve morphological and functional effects of muscular dystrophia. Dysfunction of HAT enzymes is also often associated with several diseases, including cancer; thus, the HATi can represent new chemical entities for the development of new drugs. Only a few HMTi have been described to date, but these small molecules could be a useful scaffold to discovering new highly active and enzyme-selective compounds to develop as therapeutics.
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PMID:The therapeutic uses of chromatin-modifying agents. 1750 20

Modern health care has greatly increased longevity for patients with congenital hemolytic anemias (such as sickle cell disease and thalassemia) and human immunodeficiency virus (HIV) infection. It is estimated that 10% of patients with hemoglobinopathies and 0.5% of patients with HIV infection develop moderate to severe pulmonary hypertension. Pulmonary hypertension is a relentlessly progressive disease leading to right heart failure and death. Worldwide, there are an estimated 30 million patients with sickle cell disease or thalassemia and 40 million patients with HIV disease. Considering the prevalence of pulmonary vascular disease in these populations, sickle cell disease and HIV disease may be the most common causes of pulmonary hypertension worldwide. In this review, the available data on epidemiology, hemodynamics, mechanisms, and therapeutic strategies for these diseases are summarized. Because therapy is likely to reduce morbidity and prolong survival, efforts to screen, diagnose, and treat these patients represent a global health opportunity.
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PMID:Pulmonary hypertension: an increasingly recognized complication of hereditary hemolytic anemias and HIV infection. 1846 Jun 61

An HIV-infected man receiving antiretroviral therapy-who also had lupus-like vasculitis and membranous glomerulonephritis (treated with prednisolone and azathioprine), beta-thalassaemia minor trait and post-radiotherapy functional asplenia (mimicking sickle cell disease-induced hyposplenism)-developed focal soft issue and bone infection caused by Salmonella enteritidis at the site of previous mycobacterial infection.
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PMID:Focal Salmonella enteritidis infection in a patient with HIV infection and other multiple causes of immunodeficiency. 1857 27

Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality worldwide. Progression to cirrhosis and hepatocellular carcinoma occurs in 20% of infected adults. The natural history following childhood infection is less well defined, although cirrhosis in children is described. Since blood product screening for HCV infection was introduced in 1990, most children who acquire HCV do so by vertical transmission from an infected mother. Transmission to offspring occurs in approximately 5%. Most children with HCV infection are asymptomatic. Diagnosis is made by testing those at risk for HCV RNA by polymerase chain reaction (PCR) and HCV antibody (anti-HCV) by enzyme immunoassay (EIA). The clinical impact of HCV infection is assessed by monitoring symptoms and signs, blood testing of liver enzymes, ultrasound imaging, and by liver biopsy. Improved efficacy and tolerability of treatment strategies in adults have had a significant impact on the management of children with HCV infection. The emphasis is now on promoting awareness, early diagnosis, and treatment. Treatment strategies have evolved from monotherapy with interferon alfa (IFNalpha), to combination therapy with ribavirin. Pegylated IFNalpha is superior to conventional IFNalpha, and forms the basis of current recommendations. The genotype of HCV influences treatment efficacy. Treatment is generally well tolerated in children, although adverse effects are common. Preparation and support throughout treatment for the whole family is needed. A proportion of children with HCV infection have co-morbidity, including viral co-infection or hematologic disease. Although treatment may be contraindicated, risks and benefits must be considered before denying treatment. Anemia is more common in those with HIV co-infection, renal insufficiency, thalassemia, or cirrhosis, and may be aggravated by treatment. Children with thalassemia may have iron overload, and transfusion requirements may increase during treatment. Further refinements of combination therapy and development of new drugs are in progress. Vaccine candidates are undergoing phase I and II treatment trials.
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PMID:Management strategies for hepatitis C virus infection in children. 1899 46

Growth failure is one of the most common problems in children with thalassemia with multiple etiologies. We present a case of celiac disease, an underdiagnosed cause of growth failure in a child with beta-thalassemia major. A 10-year-old boy on a hypertransfusion regimen was referred for early onset growth failure. Serology for hepatitis B, hepatitis C, and HIV was negative. Serum zinc levels were normal. Thyroid function tests and growth hormone secretion, evaluated with clonidine stimulation test were normal. Malabsorption syndrome was suspected, even in the absence of gastrointestinal symptoms. Tissue transglutaminase were highly raised >300 IU/mL (normal values <15 U/L). Characteristic mucosal lesions on jejunal biopsy confirmed the diagnosis of celiac disease. Institution of a gluten-free diet resulted in rapid gain in weight and improvement in height velocity.
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PMID:Celiac disease in a child with beta-thalassemia major: a need for improved screening and awareness. 1913 78

Osteoporosis is a remarkably frequent complication of iron loading conditions such as thalassemia, sicklemia, African siderosis, hemochromatosis, smoking, alcoholism, HIV infection, and cessation of menstruation. The metal suppresses osteoblast formation of bone and may also stimulate osteoclast resorption of bone. Iron also inhibits anterior pituitary synthesis of gonadotrophs. This, in turn, results in depressed formation of gonadal hormones. The tendency of iron-loaded persons to become osteoporotic may be enhanced by gonadal hormone deficiency. Iron binding agents that could specifically withhold excess skeletal iron (and be excreted as the iron chelate) might have therapeutic utility.
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PMID:Role of iron in osteoporosis. 1933 60

This literature review is a comprehensive summary of premarital (prenuptial) screening programmes for the most prevalent hereditary haemoglobinopathies, namely thalassaemia and sickle cell disease, and the important infections HIV (human immunodeficiency virus) and hepatitis viruses B and C (HBV and HCV). It describes the background to premarital screening programmes and their value in countries where these diseases are endemic. The use of premarital screening worldwide is critically evaluated, including recent experiences in Saudi Arabia, followed by discussion of the outcomes of such programmes. Despite its many benefits, premarital testing is not acceptable in some communities for various legal and religious reasons, and other educational and cultural factors may prevent some married couples following the advice given by counsellors. The success of these programmes therefore depends on adequate religious support, government policy, education and counselling. In contrast to premarital screening for haemoglobinopathies, premarital screening for HIV and the hepatitis viruses is still highly controversial, both in terms of ethics and cost-effectiveness. In wealthy countries, premarital hepatitis and HIV testing could become mandatory if at-risk, high-prevalence populations are clearly identified and all ethical issues are adequately addressed.
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PMID:Premarital screening programmes for haemoglobinopathies, HIV and hepatitis viruses: review and factors affecting their success. 1934 27

We report a human immunodeficiency virus-1 (HIV-1)-infected couple, where the woman in the 11th week of gestation, carried a Hb E trait. She and her spouse were referred to the hemoglobinopathy counselors. Her spouse's blood was subsequently tested and showed an increased Hb A(2) value. However, his red cell indices and osmotic fragility test were different from those found in beta-thalassemia (beta-thal) carriers. The beta-thal genes were investigated further and no mutations were observed. Therefore, it is unlikely that he is a beta-thal carrier and the increased Hb A(2) value is a result of receiving antiretroviral drugs. As antenatal thalassemia screening becomes more widespread, measuring the Hb A(2) values should be taken in all HIV-1-infected couples before the initiation of antiretroviral drugs to rule out misdiagnosis of beta-thal. However, if these tests are not available, the results of the red cell indices and osmotic fragility test should be considered as they may provide great value for beta-thal investigations.
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PMID:Increased Hb A2 values in an HIV-1-infected patient receiving antiretroviral drugs: a pitfall for thalassemia antenatal diagnosis. 1937 94

Hematopoietic stem cells (HSCs) function to provide the individual with a continuing supply of blood cells over many decades. To this end, HSCs have evolved unique mechanisms for self-preservation, including resistance to viral infection. Unfortunately, this characteristic may impede the ability to achieve high levels of gene transfer mediated by HIV-based lentiviral vectors. This is an important consideration for gene therapy efforts being undertaken for beta-thalassemia. In particular, the study of beta-thalassemia patients that underwent allogeneic stem cell transplantation and developed stable, long-term mixed chimerism suggests that HSC gene transfer levels of greater than 25% will be needed for a robust therapeutic effect in such patients. Available pre-clinical and clinical trial lentiviral gene transfer studies suggest that improvements are needed to achieve this goal. Here, we review what level of gene transfer is needed in the context of varying degrees of beta-globin deficiency, what level is currently achievable, and the areas of research which may be fruitful in improving the likelihood of success for patients with the severest forms of beta-thalassemia.
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PMID:The challenge of obtaining therapeutic levels of genetically modified hematopoietic stem cells in beta-thalassemia patients. 2071 75


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