{"id":13144,"date":"2024-08-23T04:30:40","date_gmt":"2024-08-23T02:30:40","guid":{"rendered":"https:\/\/valintermed.com\/?p=13144"},"modified":"2024-08-23T04:30:40","modified_gmt":"2024-08-23T02:30:40","slug":"defitsit-tiopurin-s-metiltransferazy","status":"publish","type":"post","link":"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/","title":{"rendered":"Thiopurine S-methyltransferase deficiency"},"content":{"rendered":"<div class=\"fpm_start\"><\/div>\n<p>Thiopurine S-methyltransferase (TPMT) deficiency is a genetic condition that involves the abnormal metabolism of thiopurines such as azathioprine and 6-mercaptopurine. This condition causes significant alterations in drug processing that can lead to severe side effects including bone marrow toxicity, decreased blood cell production, and increased risk of infections and other complications. TPMT deficiency is often found in patients receiving immunosuppressive therapy for conditions such as rheumatoid arthritis, celiac disease, and certain types of cancer. Because of variability in the genetic predisposition to this enzyme defect, treatment outcomes can vary greatly, requiring individualized treatment and monitoring.<\/p>\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_86 counter-flat ez-toc-counter ez-toc-light-blue ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Content<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewbox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 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href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%98%D1%81%D1%82%D0%BE%D1%80%D0%B8%D1%8F_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F_%D0%B8_%D0%B8%D0%BD%D1%82%D0%B5%D1%80%D0%B5%D1%81%D0%BD%D1%8B%D0%B5_%D0%B8%D1%81%D1%82%D0%BE%D1%80%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B8%D0%B5_%D1%84%D0%B0%D0%BA%D1%82%D1%8B\" >History of the disease and interesting historical facts<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%AD%D0%BF%D0%B8%D0%B4%D0%B5%D0%BC%D0%B8%D0%BE%D0%BB%D0%BE%D0%B3%D0%B8%D1%8F\" >Epidemiology<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%93%D0%B5%D0%BD%D0%B5%D1%82%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B0%D1%8F_%D0%BF%D1%80%D0%B5%D0%B4%D1%80%D0%B0%D1%81%D0%BF%D0%BE%D0%BB%D0%BE%D0%B6%D0%B5%D0%BD%D0%BD%D0%BE%D1%81%D1%82%D1%8C_%D0%BA_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%BC%D1%83_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8E\" >Genetic predisposition to this disease<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%A4%D0%B0%D0%BA%D1%82%D0%BE%D1%80%D1%8B_%D1%80%D0%B8%D1%81%D0%BA%D0%B0_%D0%B2%D0%BE%D0%B7%D0%BD%D0%B8%D0%BA%D0%BD%D0%BE%D0%B2%D0%B5%D0%BD%D0%B8%D1%8F_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%B3%D0%BE_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\" >Risk factors for the development of this disease<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%94%D0%B8%D0%B0%D0%B3%D0%BD%D0%BE%D1%81%D1%82%D0%B8%D0%BA%D0%B0_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%B3%D0%BE_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\" >Diagnosis of this disease<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%9B%D0%B5%D1%87%D0%B5%D0%BD%D0%B8%D0%B5\" >Treatment<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%A1%D0%BF%D0%B8%D1%81%D0%BE%D0%BA_%D0%BB%D0%B5%D0%BA%D0%B0%D1%80%D1%81%D1%82%D0%B2_%D0%BF%D1%80%D0%B8%D0%BC%D0%B5%D0%BD%D1%8F%D0%B5%D0%BC%D1%8B%D1%85_%D0%B4%D0%BB%D1%8F_%D0%BB%D0%B5%D1%87%D0%B5%D0%BD%D0%B8%D1%8F_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%B3%D0%BE_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\" >List of medications used to treat this disease<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%9C%D0%BE%D0%BD%D0%B8%D1%82%D0%BE%D1%80%D0%B8%D0%BD%D0%B3_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\" >Disease monitoring<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%92%D0%BE%D0%B7%D1%80%D0%B0%D1%81%D1%82%D0%BD%D1%8B%D0%B5_%D0%BE%D1%81%D0%BE%D0%B1%D0%B5%D0%BD%D0%BD%D0%BE%D1%81%D1%82%D0%B8_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\" >Age-related features of the disease<\/a><\/li><li class='ez-toc-page-1'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/valintermed.com\/en\/medlibrary\/thiopurine-methyltransferase-deficiency\/#%D0%92%D0%BE%D0%BF%D1%80%D0%BE%D1%81%D1%8B_%D0%B8_%D0%BE%D1%82%D0%B2%D0%B5%D1%82%D1%8B\" >Questions and Answers<\/a><\/li><\/ul><\/nav><\/div>\n<h2><span class=\"ez-toc-section\" id=\"%D0%98%D1%81%D1%82%D0%BE%D1%80%D0%B8%D1%8F_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F_%D0%B8_%D0%B8%D0%BD%D1%82%D0%B5%D1%80%D0%B5%D1%81%D0%BD%D1%8B%D0%B5_%D0%B8%D1%81%D1%82%D0%BE%D1%80%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B8%D0%B5_%D1%84%D0%B0%D0%BA%D1%82%D1%8B\"><\/span>History of the disease and interesting historical facts<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>Thiopurine S-methyltransferase deficiency was first described in the 1970s, when research began to identify links between thiopurine metabolism and adverse effects of treatment. Pioneers in this field included scientists such as Gaetano Palmeri and Anthony S. McAllister, who conducted important pharmacogenetic studies and established the role of TPMT in thiopurine metabolism. Their work provided insight into the mechanism of action of these drugs and paved the way for more individualized treatment approaches. Historically, the first TPMT assays were introduced into clinical practice in the early 1990s and soon became the standard for risk assessment in patients requiring thiopurine therapy.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%AD%D0%BF%D0%B8%D0%B4%D0%B5%D0%BC%D0%B8%D0%BE%D0%BB%D0%BE%D0%B3%D0%B8%D1%8F\"><\/span>Epidemiology<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>The prevalence of thiopurine S-methyltransferase deficiency varies among populations. Epidemiological studies have reported prevalence rates of complete TPMT deficiency ranging from 1:300 to 1:10,000, depending on ethnicity. For example, in Caucasians the prevalence is approximately 1:300, while in African and East Asian populations the prevalence may be significantly lower. Studies show that approximately 10% of the population has moderately decreased TPMT activity, predisposing individuals to increased toxicity with thiopurines. This highlights the importance of screening for TPMT deficiency before initiating treatment with these drugs.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%93%D0%B5%D0%BD%D0%B5%D1%82%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B0%D1%8F_%D0%BF%D1%80%D0%B5%D0%B4%D1%80%D0%B0%D1%81%D0%BF%D0%BE%D0%BB%D0%BE%D0%B6%D0%B5%D0%BD%D0%BD%D0%BE%D1%81%D1%82%D1%8C_%D0%BA_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%BC%D1%83_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8E\"><\/span>Genetic predisposition to this disease<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>TPMT deficiency is caused by mutations in the TPMT gene, which is located on chromosome 6 and is involved in the metabolism of thiopurines. The most common mutations include TPMT*2, TPMT*3A, and TPMT*3C, each of which results in varying degrees of decreased enzyme activity. These mutations result in decreased ability to metabolize and eliminate thiopurines, increasing the likelihood of toxic reactions to these drugs. Studies have found that approximately 90% patients with complete TPMT deficiency have one of these mutations, highlighting the importance of genetic testing to determine risk before initiating therapy, particularly in patients with a family history of toxic reactions to thiopurines.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%A4%D0%B0%D0%BA%D1%82%D0%BE%D1%80%D1%8B_%D1%80%D0%B8%D1%81%D0%BA%D0%B0_%D0%B2%D0%BE%D0%B7%D0%BD%D0%B8%D0%BA%D0%BD%D0%BE%D0%B2%D0%B5%D0%BD%D0%B8%D1%8F_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%B3%D0%BE_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\"><\/span>Risk factors for the development of this disease<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>Major risk factors that contribute to the development of TPMT deficiency include:<\/p>\n<ul>\n<li>Heredity - a family predisposition to mutations in the TPMT gene.<\/li>\n<li>Use of strict diets that can reduce levels of metabolic enzymes.<\/li>\n<li>Comorbid conditions that affect drug metabolism, such as liver or kidney disease.<\/li>\n<\/ul>\n<p>In addition, certain chemical and physical factors, such as chronic exposure to toxins or certain medications, may also have a negative effect on metabolic processes, increasing the risk of adverse effects when thiopurines are used in susceptible patients.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%94%D0%B8%D0%B0%D0%B3%D0%BD%D0%BE%D1%81%D1%82%D0%B8%D0%BA%D0%B0_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%B3%D0%BE_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\"><\/span>Diagnosis of this disease<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>Diagnosis of TPMT deficiency is usually based on a combination of clinical manifestations and laboratory tests. The main symptoms of deficiency include:<\/p>\n<ul>\n<li>Anemia.<\/li>\n<li>Thrombocytopenia.<\/li>\n<li>Hematological disorders such as neutropenia.<\/li>\n<\/ul>\n<p>Laboratory tests that may be used for diagnosis include:<\/p>\n<ul>\n<li>Venous blood test for blood cell levels.<\/li>\n<li>TPMT enzyme activity testing.<\/li>\n<li>Genetic testing to detect mutations in the TPMT gene.<\/li>\n<\/ul>\n<p>Radiological examinations such as therapeutic radiographs or CT scans may be ordered to rule out other conditions that may cause similar symptoms. An important step in diagnosis is differential diagnosis, which involves ruling out various causes of hematological disorders such as thrombocytopenic purpura and other confounding factors.<\/p><script data-noptimize=\"\" data-wpfc-render=\"false\">\nfpm_start( \"true\" );\n<\/script>\n\n<h2><span class=\"ez-toc-section\" id=\"%D0%9B%D0%B5%D1%87%D0%B5%D0%BD%D0%B8%D0%B5\"><\/span>Treatment<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>The treatment approach for TPMT deficiency requires an individualized approach due to significant differences in metabolism among patients. General treatment includes:<\/p>\n<ul>\n<li>Avoidance of thiopurines in patients with complete TPMT deficiency.<\/li>\n<li>If necessary, dose adjustment for patients with moderate deficiency.<\/li>\n<li>Prescribing alternative medications or therapeutic approaches.<\/li>\n<\/ul>\n<p>Pharmacological treatment may involve the use of less toxic analogues or clarification of the therapeutic regimen. Surgical treatment may be required in cases requiring immediate intervention, such as the development of a severe infection. The use of new biological agents may provide an additional therapeutic option for patients with TPMT deficiency.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%A1%D0%BF%D0%B8%D1%81%D0%BE%D0%BA_%D0%BB%D0%B5%D0%BA%D0%B0%D1%80%D1%81%D1%82%D0%B2_%D0%BF%D1%80%D0%B8%D0%BC%D0%B5%D0%BD%D1%8F%D0%B5%D0%BC%D1%8B%D1%85_%D0%B4%D0%BB%D1%8F_%D0%BB%D0%B5%D1%87%D0%B5%D0%BD%D0%B8%D1%8F_%D0%B4%D0%B0%D0%BD%D0%BD%D0%BE%D0%B3%D0%BE_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\"><\/span>List of medications used to treat this disease<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>The list of drugs used for TPMT deficiency includes:<\/p>\n<ul>\n<li>Azathioprine (with caution).<\/li>\n<li>6-mercaptopurine (with dose adjustment).<\/li>\n<li>Methotrexate.<\/li>\n<li>Prednisolone.<\/li>\n<li>Infliximab (if needed).<\/li>\n<\/ul>\n<p>These drugs require careful monitoring and control for possible side effects in patients with TPMT deficiency.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%9C%D0%BE%D0%BD%D0%B8%D1%82%D0%BE%D1%80%D0%B8%D0%BD%D0%B3_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\"><\/span>Disease monitoring<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>Monitoring of patients with TPMT deficiency includes regular follow-up examinations:<\/p>\n<ul>\n<li>Blood test for blood cell levels (every 2-4 weeks at the start of therapy).<\/li>\n<li>Genetic testing to monitor changes in TPMT activity.<\/li>\n<li>Assessment of the liver and kidneys.<\/li>\n<\/ul>\n<p>The prognosis with an individualized approach to treatment is relatively favorable, but various complications may occur, including infectious diseases, severe allergic reactions, and lymphoproliferative disorders.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%92%D0%BE%D0%B7%D1%80%D0%B0%D1%81%D1%82%D0%BD%D1%8B%D0%B5_%D0%BE%D1%81%D0%BE%D0%B1%D0%B5%D0%BD%D0%BD%D0%BE%D1%81%D1%82%D0%B8_%D0%B7%D0%B0%D0%B1%D0%BE%D0%BB%D0%B5%D0%B2%D0%B0%D0%BD%D0%B8%D1%8F\"><\/span>Age-related features of the disease<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>TPMT deficiency can manifest at any age, but symptoms often become more pronounced in childhood and adolescence, especially when treatment with thiopurines is initiated. In the elderly, such deficiency may be associated with other diseases, increasing the risks and toxicity of therapy due to polypharmacy. It is important to consider physical condition, the presence of comorbidities, and the overall metabolic state when planning treatment.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"%D0%92%D0%BE%D0%BF%D1%80%D0%BE%D1%81%D1%8B_%D0%B8_%D0%BE%D1%82%D0%B2%D0%B5%D1%82%D1%8B\"><\/span>Questions and Answers<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<ul>\n<li><strong>What is thiopurine S-methyltransferase deficiency?<\/strong> This is a genetic condition associated with a defect in the metabolism of thiopurines, which leads to an increased likelihood of toxic effects when using these drugs.<\/li>\n<li><strong>What are the symptoms of TPMT deficiency?<\/strong> The main symptoms include anemia, thrombocytopenia and other hematological disorders.<\/li>\n<li><strong>How is TPMT deficiency diagnosed?<\/strong> Diagnosis includes blood tests to check blood cell levels, TPMT enzyme activity testing, and genetic testing.<\/li>\n<li><strong>How is TPMT deficiency treated?<\/strong> Treatment involves avoiding thiopurines in patients with complete deficiency and adjusting doses in patients with moderate deficiency.<\/li>\n<li><strong>What are the risk factors for the disease?<\/strong> Risk factors include heredity, comorbid conditions and certain chemical factors that contribute to drug metabolism disorders.<\/li>\n<\/ul>\n<div class=\"fpm_end\"><\/div>","protected":false},"excerpt":{"rendered":"<p>Thiopurine S-methyltransferase (TPMT) deficiency is a genetic condition that involves impaired metabolism of thiopurines such as azathioprine and 6-mercaptopurine. It<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[298],"tags":[],"class_list":["post-13144","post","type-post","status-publish","format-standard","hentry","category-medlibrary"],"_links":{"self":[{"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts\/13144","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/comments?post=13144"}],"version-history":[{"count":1,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts\/13144\/revisions"}],"predecessor-version":[{"id":13776,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts\/13144\/revisions\/13776"}],"wp:attachment":[{"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/media?parent=13144"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/categories?post=13144"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/tags?post=13144"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}