{"id":13352,"date":"2024-08-23T01:00:54","date_gmt":"2024-08-22T23:00:54","guid":{"rendered":"https:\/\/valintermed.com\/?p=13352"},"modified":"2024-08-23T01:00:54","modified_gmt":"2024-08-22T23:00:54","slug":"narusheniya-tsikla-mocheviny-ntsm","status":"publish","type":"post","link":"https:\/\/valintermed.com\/en\/medlibrary\/ntsm-urea-cycle-disturbances\/","title":{"rendered":"Urea cycle disorders (UCD)"},"content":{"rendered":"<div class=\"fpm_start\"><\/div>\n<p>Urea cycle disorders (UCDs) are inherited metabolic disorders that are caused by a deficiency in one or more enzymes responsible for metabolizing ammonia and converting it into urea in the liver. The disease results in a buildup of toxic ammonia in the body, which can lead to severe neurological impairment and, in extreme cases, death. UCDs can present in various age groups, most commonly beginning in infancy or early childhood. Symptoms range from mild clinical manifestations to critical conditions requiring emergency medical care. Treatment of UCDs requires a multidisciplinary approach, including dietary therapy, medication, and, in some cases, surgery to reduce ammonia levels and prevent its toxic effects.<\/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 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href=\"https:\/\/valintermed.com\/en\/medlibrary\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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\/ntsm-urea-cycle-disturbances\/#%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>The history of the study of urea cycle disorders began in the mid-20th century, when scientists began to identify associations between certain enzyme deficiencies and clinical manifestations of the disease. The first identified urea cycle disorders were carbamoyl phosphate synthetase I deficiency, which was described in the 1960s. Since then, other enzymes involved in this metabolic process have been discovered, including ornithine transcarbamylase, argininosuccinate synthetase, and argininosuccinate lyase. Research has revealed the possibility of a genetic predisposition to UCD, which has facilitated the development of molecular diagnostics and therapeutics. Historical cases have also been studied, such as a surge in childhood cases in Denmark in the 1970s due to mutations in genes encoding enzymes, which has led to public health efforts to screen and diagnose UCD early.<\/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>Urea cycle disorders occur with an incidence of approximately 1 in 30,000\u201350,000 births worldwide. However, the incidence rate may vary by population and ethnicity. For example, in some areas with a high incidence of consanguinity, such as the Middle East, the incidence may be as high as 1 in 10,000. Also, the overall incidence may be higher among certain ethnic groups due to hereditary predispositions. An important aspect is that many cases of UCD remain uninvestigated and undiagnosed, as the manifestations of the disease may be quite non-specific or mild.<\/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>Urea cycle disorders usually result from mutations in one of the genes encoding enzymes involved in the utilization of ammonia. The most significant mutations are in the following genes:<\/p>\n<ul>\n<li>CPS1 is the gene encoding carbamoyl phosphate synthetase I;<\/li>\n<li>OTC - encodes ornithine transcarbamylase;<\/li>\n<li>ASS1\u2014argininosuccinate synthetase gene;<\/li>\n<li>ASL - encodes argininosuccinate lyase;<\/li>\n<li>ARG1\u2014arginase gene.<\/li>\n<\/ul>\n<p>Each of these mutations can lead to specific clinical symptoms and disease severity. The disease is inherited in an autosomal recessive manner, meaning that both parents must be carriers of the mutation for their child to inherit the disease. Genetic testing can identify carriers and assess the risk of disease transmission in family practice.<\/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>The main risk factors for the development of NCM include:<\/p>\n<ul>\n<li>Heredity - the presence of cases of NCM in the family;<\/li>\n<li>Consanguinity is the birth of children from blood relatives;<\/li>\n<li>Availability of modern diagnostics and screening in the population;<\/li>\n<li>Genetic predisposition - the presence of abnormalities in genes associated with the urea cycle.<\/li>\n<\/ul>\n<p>There are no external physical or chemical factors that directly cause NCM, but some environmental factors can aggravate the manifestations of the disease in those already infected.<\/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 urea cycle disorders involves examination of clinical symptoms and laboratory tests to determine whether there is an increase in ammonia and other metabolites. The main symptoms of UCD include:<\/p>\n<ul>\n<li>Neurological disorders - lethargy, confusion, seizures;<\/li>\n<li>Increased fatigue and drowsiness;<\/li>\n<li>Vomiting and refusal to eat;<\/li>\n<li>Unusual breath odor (such as ammonia);<\/li>\n<li>Development of alternating psychomotor states.<\/li>\n<\/ul>\n<p>Laboratory tests include:<\/p><script data-noptimize=\"\" data-wpfc-render=\"false\">\nfpm_start( \"true\" );\n<\/script>\n\n<ul>\n<li>Determination of the level of ammonia in the blood;<\/li>\n<li>Blood test for amino and organic acids;<\/li>\n<li>Molecular genetic testing to identify mutations in gene abnormalities.<\/li>\n<\/ul>\n<p>Radiological examinations such as abdominal ultrasound may help to exclude other pathologies. The differential diagnosis of NCM includes other metabolic disorders such as glucose-galactose malabsorption and various forms of primary hypometabolic encephalopathy.<\/p>\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>Treatment of urea cycle disorders involves a number of strategies to reduce ammonia levels and improve metabolism. Common approaches include:<\/p>\n<ul>\n<li>Diet therapy - limiting protein intake and using formulas that provide the required amount of essential amino acids;<\/li>\n<li>Pharmacological treatment - the use of medications that reduce the level of ammonia in the blood and promote the elimination of toxic metabolites (for example, sodium zabreconic acid);<\/li>\n<li>Hemodialysis or peritoneal dialysis - used in severe cases to quickly reduce ammonia levels;<\/li>\n<li>Surgical treatment - in rare cases, surgical intervention may be performed to correct hepatic vein anastomoses, which reduces the toxic load.<\/li>\n<\/ul>\n<p>Complex treatment requires an individual approach and monitoring of the patient\u2019s condition, especially in acute conditions.<\/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>Among the main drugs used to treat NCM, the following can be distinguished:<\/p>\n<ul>\n<li>Levocarnitine;<\/li>\n<li>Sodium zabreconic acid;<\/li>\n<li>Argininosuccinate;<\/li>\n<li>Sodium benzoate;<\/li>\n<li>Symptomatic drugs for the elimination of neurological disorders.<\/li>\n<\/ul>\n<p>Medicines are selected and used depending on the severity of the patient&#039;s condition and current clinical manifestations. <\/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 NCM includes regular monitoring of ammonia concentration in the blood, which allows timely prevention of its accumulation and associated complications. Other important aspects of monitoring include:<\/p>\n<ul>\n<li>Regular laboratory tests to assess metabolic status;<\/li>\n<li>Following a strict diet and monitoring protein intake;<\/li>\n<li>Assessment of neurological status to identify possible abnormalities;<\/li>\n<li>Creating an individual treatment plan based on the patient&#039;s current health condition.<\/li>\n<\/ul>\n<p>The prognosis depends on the number of cases and the severity of symptoms. Early diagnosis and adequate treatment can significantly improve quality of life and reduce the risk of complications.<\/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>Urea cycle disorders may manifest at different age periods. In newborns, symptoms may appear from the first days of life, including severe neurological disorders and death if the diagnosis is not established in time. In older children, less pronounced clinical manifestations are often observed, which can complicate the diagnosis. In adult patients, UCD may manifest as a result of systemic stress on the liver, which implies the need for regular monitoring and control.<\/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 are urea cycle disorders?<\/strong> Urea cycle disorders are inherited metabolic disorders that involve a deficiency of enzymes needed to metabolize ammonia in the liver, resulting in its accumulation in the body.<\/li>\n<li><strong>How are NCMs diagnosed?<\/strong> Diagnosis is based on clinical symptoms, blood ammonia levels, and molecular genetic testing to detect mutations in the relevant genes.<\/li>\n<li><strong>How is NCM treated?<\/strong> Treatment includes diet therapy, pharmacological support, and, if necessary, hemodialysis and surgical interventions.<\/li>\n<li><strong>What are the possible consequences and prognosis for NCM?<\/strong> With adequate diagnosis and treatment, the prognosis can be satisfactory, but if you seek medical attention late, serious complications are possible.<\/li>\n<li><strong>What is the genetic predisposition to NCM?<\/strong> NCM is inherited in an autosomal recessive manner; mutations can be found in various genes that disrupt ammonia metabolism.<\/li>\n<\/ul>\n<div class=\"fpm_end\"><\/div>","protected":false},"excerpt":{"rendered":"<p>Urea cycle disorders (UCDs) are inherited metabolic disorders that are associated with a deficiency of one or more enzymes responsible for the utilization of<\/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-13352","post","type-post","status-publish","format-standard","hentry","category-medlibrary"],"_links":{"self":[{"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts\/13352","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=13352"}],"version-history":[{"count":1,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts\/13352\/revisions"}],"predecessor-version":[{"id":13566,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/posts\/13352\/revisions\/13566"}],"wp:attachment":[{"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/media?parent=13352"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/categories?post=13352"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/valintermed.com\/en\/wp-json\/wp\/v2\/tags?post=13352"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}