{"id":112069,"date":"2025-06-17T11:09:06","date_gmt":"2025-06-17T02:09:06","guid":{"rendered":"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/"},"modified":"2025-08-22T17:23:10","modified_gmt":"2025-08-22T08:23:10","slug":"homocystinuria-cbs-deficiency-overview","status":"publish","type":"post","link":"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en","title":{"rendered":"Cystathionine Beta-Synthase Deficiency and Homocystinuria"},"content":{"rendered":"\n<div style=\"height:20px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div style=\"border: 4px solid #e9e4f5; background-color: #fcfbff; border-radius: 12px; padding: 1.5rem; margin: 1.5rem 0 2.5rem; font-family: 'Helvetica Neue', sans-serif; line-height: 1.6; box-shadow: 0 2px 8px rgba(0, 0, 0, 0.03);\">\n  <div id=\"ez-toc-container\" class=\"ez-toc-v2_0_82_2 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">\u76ee\u6b21<\/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 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#%E3%82%84%E3%81%95%E3%81%97%E3%81%84%E3%81%BE%E3%81%A8%E3%82%81\" >\u3084\u3055\u3057\u3044\u307e\u3068\u3081<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Implicated_Genomic_Region\" >Implicated Genomic Region<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Overview\" >Overview<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Symptoms\" >Symptoms<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Diagnosis\" >Diagnosis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Treatment_and_Management\" >Treatment and Management<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Prognosis\" >Prognosis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Genetic_Counseling\" >Genetic Counseling<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#Helpful_Terms\" >Helpful Terms<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\/#References\" >References<\/a><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n<h2 style=\"margin-top: 0; margin-bottom: 0.75rem; font-size: 1.25rem; color: #7e6cae; text-align: left; border: none; border-bottom: none; padding-bottom: 0; display: block;\"><span class=\"ez-toc-section\" id=\"%E3%82%84%E3%81%95%E3%81%97%E3%81%84%E3%81%BE%E3%81%A8%E3%82%81\"><\/span>\u3084\u3055\u3057\u3044\u307e\u3068\u3081<span class=\"ez-toc-section-end\"><\/span><\/h2>\n  <p style=\"margin: 0; font-size: 1rem; color: #444;\">\n  This article breaks down the science behind cystathionine beta-synthase (CBS) deficiency, also known as homocystinuria. It covers how the condition develops, the wide range of symptoms it causes, methods for early detection, and available treatment options. Readers will also find practical insights on prognosis, genetic counseling, and supportive care.\n  <\/p>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Implicated_Genomic_Region\"><\/span>Implicated Genomic Region<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<div style=\"height:18px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"has-text-align-center\"><strong>CBS<\/strong><\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"26\" src=\"\/nipt\/wp-content\/uploads\/2025\/06\/CBS-hgtIdeo_genome_asia_3f7ee_fbb500-1024x26.png\" alt=\"CBS\" class=\"wp-image-101419\"\/><\/figure><\/div>\n\n\n<div style=\"height:18px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Overview\"><\/span><strong>Overview<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Homocystinuria, also known as cystathionine beta-synthase (CBS) deficiency, is a rare inherited metabolic disorder caused by mutations in the <strong>CBS gene<\/strong>. This gene encodes the enzyme cystathionine beta-synthase, which plays a key role in the metabolism of sulfur-containing amino acids. Specifically, the enzyme facilitates the conversion of homocysteine to cystathionine in the transsulfuration pathway.<\/p>\n\n\n\n<p>When CBS activity is deficient or absent, homocysteine builds up in the blood and urine. Elevated homocysteine disrupts several systems in the body, affecting the eyes, bones, vascular system, and nervous system.<\/p>\n\n\n\n<p>CBS deficiency follows an <strong>autosomal recessive inheritance pattern<\/strong>, meaning a child must inherit one mutated copy of the gene from each parent to develop the condition.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Symptoms\"><\/span><strong>Symptoms<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Eye Symptoms<\/strong><\/h4>\n\n\n\n<p>One of the most consistent findings in homocystinuria is <strong>ectopia lentis<\/strong>, the displacement of the eye\u2019s lens. This usually develops between the ages of one and eight. Severe myopia, or extreme nearsightedness, is also common, contributing to significant vision problems early in life.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Skeletal Abnormalities<\/strong><\/h4>\n\n\n\n<p>Many individuals exhibit a <strong>marfanoid habitus<\/strong>, characterized by tall stature and unusually long limbs. Other musculoskeletal complications include scoliosis, or abnormal curvature of the spine, and <strong>osteoporosis<\/strong>, which makes bones fragile and more prone to fractures.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Vascular Issues<\/strong><\/h4>\n\n\n\n<p>The vascular system is especially vulnerable to high homocysteine levels. <strong>Thromboembolism<\/strong>, or the formation of blood clots in veins, lungs, or the brain, is a serious complication and a leading cause of morbidity. These risks increase during pregnancy or periods of immobility.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Neurological and Psychiatric Issues<\/strong><\/h4>\n\n\n\n<p>Neurological involvement varies in severity. Many individuals experience <strong>intellectual disability<\/strong> or developmental delays. Seizures are not uncommon, and psychiatric conditions such as anxiety, obsessive-compulsive behavior, and depression are frequently reported.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Other Symptoms<\/strong><\/h4>\n\n\n\n<p>Additional signs may include <strong>hypopigmentation<\/strong> of the skin and hair, producing lighter coloring. Some individuals show a characteristic <strong>malar flush<\/strong>, a reddish tint in the face. Rare complications such as pancreatitis or liver cysts have also been documented.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosis\"><\/span><strong>Diagnosis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Biochemical Testing<\/strong><\/h4>\n\n\n\n<p>Biochemical assays are the first step in diagnosis. Plasma homocysteine levels are typically very high, often above 100 \u00b5mol\/L. Methionine levels in the blood are usually elevated, and urine tests reveal increased homocystine excretion.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Genetic Testing<\/strong><\/h4>\n\n\n\n<p>Genetic sequencing of the <strong>CBS gene<\/strong> can confirm the diagnosis, identifying pathogenic variants in approximately 96% of cases.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Newborn Screening<\/strong><\/h4>\n\n\n\n<p>Many regions include homocystinuria in their newborn screening panels. A heel-prick blood sample is analyzed for elevated methionine levels. If levels are high, follow-up testing confirms whether the infant has elevated homocystine.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Pyridoxine Responsiveness Test<\/strong><\/h4>\n\n\n\n<p>A pyridoxine (vitamin B6) challenge helps determine whether the patient is responsive to this treatment. A positive response indicates that high-dose pyridoxine supplementation may effectively reduce homocysteine levels.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Treatment_and_Management\"><\/span><strong>Treatment and Management<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Although there is no definitive cure, multiple strategies can manage symptoms and reduce complications.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Vitamin B6 (Pyridoxine) Supplementation<\/strong><\/h4>\n\n\n\n<p>In pyridoxine-responsive patients, high doses of vitamin B6, typically between 200 and 1000 mg per day, can substantially reduce homocysteine levels.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Methionine-Restricted Diet<\/strong><\/h4>\n\n\n\n<p>A diet low in methionine, supplemented with specialized amino acid formulas to ensure adequate nutrition, helps control homocysteine buildup.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Betaine<\/strong><\/h4>\n\n\n\n<p>Betaine is often prescribed to enhance the conversion of homocysteine into methionine, thereby lowering toxic homocysteine levels in the bloodstream.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Folic Acid and Vitamin B12 Supplementation<\/strong><\/h4>\n\n\n\n<p>Folic acid and vitamin B12 support the remethylation pathway, helping recycle homocysteine into methionine, which further aids in maintaining safer metabolic levels.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Thrombosis Risk Management<\/strong><\/h4>\n\n\n\n<p>Individuals with high clotting risk, such as those undergoing surgery or pregnancy, may be treated with low molecular weight heparin or low-dose aspirin to reduce the chance of thrombotic events.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Liver Transplant<\/strong><\/h4>\n\n\n\n<p>In rare, severe cases where metabolic control cannot be achieved with standard therapies, a <strong>liver transplant<\/strong> may be considered. The transplanted liver provides a source of functional CBS enzyme.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Supportive Therapies<\/strong><\/h4>\n\n\n\n<p>Regular follow-up is vital. Physical therapy can support musculoskeletal health, speech therapy may assist with communication delays, and psychiatric care is recommended for managing behavioral and mental health challenges.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognosis\"><\/span><strong>Prognosis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>The outlook for homocystinuria depends on early detection and consistent management. Individuals diagnosed and treated in early childhood, particularly those responsive to pyridoxine, can often avoid most complications and achieve normal growth and cognitive development.<\/p>\n\n\n\n<p>Without treatment, the condition can lead to progressive intellectual disability, significant skeletal deformities, and life-threatening vascular events, often resulting in reduced life expectancy.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Genetic_Counseling\"><\/span><strong>Genetic Counseling<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Genetic counseling is strongly advised for families affected by homocystinuria. With autosomal recessive inheritance, there is a 25% chance that each child of two carriers will inherit both defective copies of the gene and develop the disorder. Family members may be offered carrier testing, and prospective parents can consider prenatal diagnostic options such as chorionic villus sampling (CVS) or amniocentesis.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Helpful_Terms\"><\/span><strong>Helpful Terms<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Homocysteine<\/strong>: An amino acid that, when excessively elevated, damages blood vessels, bones, and connective tissues.<br><strong>Pyridoxine (Vitamin B6)<\/strong>: A vitamin that supports the CBS enzyme and can reduce homocysteine levels in responsive cases.<br><strong>Betaine<\/strong>: A compound that facilitates the conversion of homocysteine into methionine, reducing the harmful effects of high homocysteine.<br><strong>Ectopia Lentis<\/strong>: Displacement of the eye lens, commonly observed in homocystinuria.<br><strong>Marfanoid Habitus<\/strong>: A body shape characterized by tall stature and long limbs, often linked to connective tissue abnormalities in this condition.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"References\"><\/span><strong>References<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Sacharow SJ, Picker JD, Levy HL. <em>Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency<\/em>. GeneReviews. 2004.<br>Majtan T, et al. <em>Recent Therapeutic Approaches to Cystathionine Beta\u2010Synthase\u2010Deficient Homocystinuria<\/em>. British Journal of Pharmacology. 2023.<br>Liu X, et al. <em>Identification and Functional Analysis of Cystathionine Beta-Synthase Gene Mutations<\/em>. Biomedicines. 2025.<\/p>\n\n\n\n<!-- \u3042\u3044\u3046\u3048\u304a\u304b\u304d\u304f\u3051\u3053\u3055\u3057\u3059\u305b\u305d\u305f\u3061\u3064\u3066\u3068-->\n\n<script type=\"application\/ld+json\">\n{\n  \"@context\": \"https:\/\/schema.org\",\n  \"@type\": \"Article\",\n  \"mainEntityOfPage\": {\n    \"@type\": \"WebPage\",\n    \"@id\": \"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\"\n  },\n  \"headline\": \"\u30db\u30e2\u30b7\u30b9\u30c1\u30f3\u5c3f\u75c7\uff08CBS\u6b20\u640d\u75c7\uff09\u306e\u75c7\u72b6\u3068\u6cbb\u7642\uff5c\u30d2\u30ed\u30af\u30ea\u30cb\u30c3\u30af\",\n  \"description\": 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href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/homocystinuria-cbs-deficiency-overview\/?lang=en\">\u7d9a\u304d\u3092\u8aad\u3080<\/a>","protected":false},"author":79,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[97],"tags":[],"class_list":["post-112069","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/112069","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/users\/79"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/comments?post=112069"}],"version-history":[{"count":2,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/112069\/revisions"}],"predecessor-version":[{"id":112081,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/112069\/revisions\/112081"}],"wp:attachment":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media?parent=112069"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/categories?post=112069"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/tags?post=112069"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}