{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:11:51Z","timestamp":1791137511364,"version":"4.1.0"},"reference-count":34,"publisher":"BMJ","issue":"7064","license":[{"start":{"date-parts":[[1996,10,26]],"date-time":"1996-10-26T00:00:00Z","timestamp":846288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ"],"accepted":{"date-parts":[[1996,8,20]]},"published-print":{"date-parts":[[1996,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Objective<\/jats:bold>\n                    : To assess the causes for delay in the diagnosis of homocystinuria.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Design<\/jats:bold>\n                    : Clinical and laboratory data were collected from patients diagnosed as having homocystinuria due to cystathionine synthase deficiency, with special reference to the ages at which the patients had their first major signs of the disease, ectopia lentis was established, and homocystinuria was diagnosed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Setting<\/jats:bold>\n                    : University hospital in the Netherlands.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Subjects<\/jats:bold>\n                    : 34 patients (18 males) in whom homocystinuria due to cystathionine synthase deficiency was diagnosed in the period 1970\u201394.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Among 34 consecutively detected homocystinuria patients the mean age at diagnosis of homocystinuria was 24 (range 1\u201361) years. Despite frequent ocular manifestations, serious complications in the vascular, skeletal, and central nervous systems, and repeated examinations performed in these patients by clinicians of various disciplines, there was a mean delay of 11 (0\u201343) years between the first major signs of the disease (at mean age 13 (1\u201340) years) and the ultimate diagnosis of homocystinuria. Even when ectopia lentis was diagnosed (in 26 (76%) patients, mean age 18 (1\u201350) years), this did not lead to adequate biochemical analysis for homocystinuria at the time of detection, causing a mean diagnostic delay of 8 (0\u201324) years in these patients.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    : Three factors should have precipitated the diagnosis of homocystinuria: early recognition that unusual myopia (high, very high, abnormal progressive, or at young age) was caused by subluxation of the ocular lenses; awareness that the occurrence of myopia combined with systemic complications (\u201cmyopia plus\u201d) might be due to homocystinuria; and appropriate biochemical investigations carried out in patients with ectopia lentis and in their siblings.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text position=\"float\">\n                      <jats:sec>\n                        <jats:title>Key messages<\/jats:title>\n                        <jats:list list-type=\"bullet\">\n                          <jats:list-item>\n                            <jats:p>High myopia may be caused by ectopia lentis<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Unusual myopia combined with skeletal, vascular, or central nervous system manifestations may have its origin in homocystinuria<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Patients with ectopia lentis should have appro- priate blood examinations for homocystinuria<\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:sec>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1136\/bmj.313.7064.1037","type":"journal-article","created":{"date-parts":[[2011,10,31]],"date-time":"2011-10-31T16:59:58Z","timestamp":1320080398000},"page":"1037-1040","source":"Crossref","is-referenced-by-count":59,"title":["Delay in diagnosis of homocystinuria: retrospective study of consecutive patients"],"prefix":"10.1136","volume":"313","author":[{"given":"Johan R M","family":"Cruysberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godfried H J","family":"Boers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M Frans","family":"Trijbels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"August F","family":"Deutman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,10,26]]},"reference":[{"key":"2025122311452050000_313.7064.1037.1","unstructured":"Mudd SH Levy HL Skovby F . Disorders of transsulfuration. In: Scriver ChR Beaudet AL Sly WS Valle D eds. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 1995:1279\u2013327."},{"key":"2025122311452050000_313.7064.1037.2","first-page":"1","article-title":"The natural history of homocystinuria due to cystathionine beta-synthase deficiency","volume":"37","author":"Mudd","year":"1985","journal-title":"Am J Hum Genet"},{"key":"2025122311452050000_313.7064.1037.3","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(83)90049-5"},{"key":"2025122311452050000_313.7064.1037.4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00293290"},{"key":"2025122311452050000_313.7064.1037.5","doi-asserted-by":"crossref","unstructured":"Boers GHJ . Homocystinuria. Dortdrecht and Riverton, WY: Foris, 1986. 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St Louis: Mosby, 1972:224\u201381."},{"key":"2025122311452050000_313.7064.1037.17","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1302\/0301-620X.54B2.277","article-title":"Homocystinuria and Marfan's syndrome: a comparison","volume":"54B","author":"Brenton","year":"1972","journal-title":"J Bone Joint Surg"},{"key":"2025122311452050000_313.7064.1037.18","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1136\/adc.37.195.505","article-title":"Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland","volume":"37","author":"Carson","year":"1962","journal-title":"Arch Dis Child"},{"key":"2025122311452050000_313.7064.1037.19","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(62)90114-6"},{"key":"2025122311452050000_313.7064.1037.20","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1967.00980030291006"},{"key":"2025122311452050000_313.7064.1037.21","first-page":"167","article-title":"L'homocystinurie et le syndrome de Marfan","volume":"205","author":"Cernea","year":"1972","journal-title":"Ann d'Oculist"},{"key":"2025122311452050000_313.7064.1037.22","first-page":"128","article-title":"Dislocation of the lens in Marfan's syndrome. 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