{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:35:59Z","timestamp":1793709359168,"version":"4.6.1"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nutricia Metabolics"},{"DOI":"10.13039\/501100009553","name":"Czech Health Research Council","doi-asserted-by":"crossref","award":["NV19-01-00307"],"award-info":[{"award-number":["NV19-01-00307"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016366","name":"General University Hospital in Prague","doi-asserted-by":"crossref","award":["RVO-VFN 64165"],"award-info":[{"award-number":["RVO-VFN 64165"]}],"id":[{"id":"10.13039\/501100016366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>HCU Network Australia is one of the very few support groups for patients with homocystinurias. Here we report the results of its survey of 143 patients and caregivers from 22 countries, evaluating current diagnostic pathways and management for the homocystinurias. Most (110) of the responses related to patients with CBS deficiency. The diagnosis was made by newborn screening in 20% of patients and in 50% of the others within 1\u00a0year of the initial symptom but in 12.5% it took over 15\u00a0years. The delay was attributed mainly to ignorance of the disease. Physicians need to learn to measure homocysteine concentrations in children with neurodevelopmental problems, and in patients with heterogeneous symptoms such as thromboembolism, dislocation of the optic lens, haemolytic uraemic syndrome, and psychiatric disease. Even when the diagnosis is made, the way it is communicated is sometimes poor. Early-onset CBS deficiency usually requires a low-protein diet with amino acid supplements. More than a third of the participants reported problems with the availability or cost of treatment. Only half of the patients always took their amino acid mixture. In contrast, good adherence to the protein restriction was reported in 98% but 80% said it was hard, time-consuming and caused unhappiness.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>There is often a long delay in diagnosing the homocystinurias unless this is achieved by newborn screening; this survey also highlights problems with the availability and cost of treatment and the palatability of protein substitutes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-01764-x","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T11:04:04Z","timestamp":1615374244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction"],"prefix":"10.1186","volume":"16","author":[{"given":"T.","family":"Morrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"B\u00f6sch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Landolt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Ko\u017eich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0590-678X","authenticated-orcid":false,"given":"M.","family":"Huemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. A. M.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"1764_CR1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/978-3-642-40337-8_13","volume-title":"Physician's guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases","author":"MR Baumgartner","year":"2014","unstructured":"Baumgartner MR, Fowler B. Vitamin B12 disorders. In: Blau N, Duran M, Gibson KM, Dionisi Vici C, editors. Physician\u2019s guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Berlin: Springer; 2014. p. 205\u201318."},{"issue":"6","key":"1764_CR2","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1007\/s10545-014-9729-0","volume":"37","author":"S Moorthie","year":"2014","unstructured":"Moorthie S, Cameron L, Sagoo GS, et al. Systematic review and meta-analysis to estimate the birth prevalence of five inherited metabolic diseases. J Inherit Metab Dis. 2014;37(6):889\u201398.","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"1764_CR3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10545-016-9991-4","volume":"40","author":"M Huemer","year":"2017","unstructured":"Huemer M, Diodato D, Schwahn B, et al. Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency. J Inherit Metab Dis. 2017;40(1):21\u201348.","journal-title":"J Inherit Metab Dis"},{"key":"1764_CR4","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/978-3-642-40337-8_10","volume-title":"Physician's guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases","author":"F Scaglia","year":"2014","unstructured":"Scaglia F, Blau N. Disorders of folate metabolism and transport. In: Blau N, Duran M, Gibson KM, Dionisi Vici C, editors. Physician\u2019s guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Berlin: Springer; 2014. p. 167\u201378."},{"key":"1764_CR5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/8904_2016_529","volume":"29","author":"L Knowles","year":"2016","unstructured":"Knowles L, Morris AAM, Walter JH. Treatment with mefolinate (5-methyltetrahydrofolate), but not folic acid or folinic acid, leads to measurable 5-methyltetrahydrofolate in cerebrospinal fluid in methylenetetrahydrofolate reductase deficiency. JIMD Rep. 2016;29:103\u20137.","journal-title":"JIMD Rep"},{"issue":"1","key":"1764_CR6","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s10545-016-9979-0","volume":"40","author":"AAM Morris","year":"2017","unstructured":"Morris AAM, Ko\u017eich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017;40(1):49\u201374.","journal-title":"J Inherit Metab Dis"},{"key":"1764_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12338","author":"V Ko\u017eich","year":"2020","unstructured":"Ko\u017eich V, Sokolov\u00e1 J, Morris AAM, et al. Cystathionine \u03b2-synthase deficiency in the E-HOD registry-part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis. J Inherit Metab Dis. 2020. https:\/\/doi.org\/10.1002\/jimd.12338.","journal-title":"J Inherit Metab Dis."},{"issue":"1","key":"1764_CR8","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/jimd.12034","volume":"42","author":"R Keller","year":"2019","unstructured":"Keller R, Chrastina P, Pavl\u00edkov\u00e1 M, et al. Newborn screening for homocystinurias: recent recommendations versus current practice. J Inherit Metab Dis. 2019;42(1):128\u201339.","journal-title":"J Inherit Metab Dis"},{"issue":"7","key":"1764_CR9","doi-asserted-by":"publisher","first-page":"376","DOI":"10.12968\/bjon.2014.23.7.376","volume":"23","author":"M Hooper","year":"2014","unstructured":"Hooper M, Hudson P, Porter F, McCaddon A. Patient journeys: diagnosis and treatment of pernicious anaemia. Br J Nurs. 2014;23(7):376\u201381. https:\/\/doi.org\/10.12968\/bjon.2014.23.7.376.","journal-title":"Br J Nurs"},{"key":"1764_CR10","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1750-1172-8-22","volume":"8","author":"M Anderson","year":"2013","unstructured":"Anderson M, Elliott EJ, Zurynski YA. Australian families living with rare disease: experiences of diagnosis, health services use and needs for psychosocial support. Orphanet J Rare Dis. 2013;8:22.","journal-title":"Orphanet J Rare Dis"},{"key":"1764_CR11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ymgmr.2018.10.002","volume":"17","author":"S Ford","year":"2018","unstructured":"Ford S, O\u2019Driscoll M, MacDonald A. Living with Phenylketonuria: Lessons from the PKU community. Mol Genet Metab Rep. 2018;17:57\u201363.","journal-title":"Mol Genet Metab Rep"},{"key":"1764_CR12","unstructured":"IBM Corp. IBM SPSS Statistics for Windows. 2016."},{"issue":"2","key":"1764_CR13","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/jimd.12041","volume":"42","author":"M Huemer","year":"2019","unstructured":"Huemer M, Diodato D, Martinelli D, et al. Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: data from the E-HOD registry. J Inherit Metab Dis. 2019;42(2):333\u201352.","journal-title":"J Inherit Metab Dis"},{"issue":"6","key":"1764_CR14","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1002\/jimd.12066","volume":"42","author":"F Molema","year":"2019","unstructured":"Molema F, Gleich F, Burgard P, et al. Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders: on the basis of information from a European multicenter registry. J Inherit Metab Dis. 2019;42(6):1162\u201375.","journal-title":"J Inherit Metab Dis"},{"issue":"2","key":"1764_CR15","doi-asserted-by":"publisher","first-page":"e0172532","DOI":"10.1371\/journal.pone.0172532","volume":"12","author":"S Bl\u00f6\u00df","year":"2017","unstructured":"Bl\u00f6\u00df S, Klemann C, Rother AK, et al. Diagnostic needs for rare diseases and shared prediagnostic phenomena: results of a German-wide expert Delphi survey. PLoS ONE. 2017;12(2):e0172532.","journal-title":"PLoS ONE"},{"key":"1764_CR16","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1136\/bmj.313.7064.1037","volume":"313","author":"JR Cruysberg","year":"1996","unstructured":"Cruysberg JR, Boers GH, Trijbels JM, Deutman AF. Delay in diagnosis of homocystinuria: retrospective study of consecutive patients. BMJ. 1996;313:1037\u201340.","journal-title":"BMJ"},{"issue":"1","key":"1764_CR17","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1186\/s13023-019-1236-9","volume":"14","author":"NA Zeltner","year":"2019","unstructured":"Zeltner NA, Welsink-Karssies MM, Landolt MA, et al. Reducing complexity: explaining inborn errors of metabolism and their treatment to children and adolescents. Orphanet J Rare Dis. 2019;14(1):248.","journal-title":"Orphanet J Rare Dis."},{"key":"1764_CR18","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12301","author":"F B\u00f6sch","year":"2020","unstructured":"B\u00f6sch F, Landolt MA, Baumgartner MR, et al. Health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism: analysis of an international data set. J Inherit Metab Dis. 2020. https:\/\/doi.org\/10.1002\/jimd.12301.","journal-title":"J Inherit Metab Dis."}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01764-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-021-01764-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01764-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T11:14:41Z","timestamp":1615374881000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-01764-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,10]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1764"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-01764-x","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,10]]},"assertion":[{"value":"19 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). The study was initiated and carried out by patient organization HCU Network Australia, data were anonymous and no ethics committee approval was sought. The \u201cKantonale Ethikkommission Z\u00fcrich\u201d raised no concern regarding statistical analysis of the anonymised survey data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MH, AAMM, MAL, VK, TM and FB declare no conflicts of interest regarding the contents of this manuscript. MH has received research grants from Nutricia Metabolics and SOBI and honoraria for lectures or scientific advice from Nutricia Metabolics, Recordati Rare Disease Foundation, Shire, Aeglea and Sanofi Genzyme. AAMM has received honoraria for lectures from Recordati & Nutricia and Advisory Board fees from Nutricia. FB has received research grants from Nutricia Metabolics. VK declares that Charles University-First Faculty of Medicine received in the past a partial reimbursement for preclinical testing of OT-58 from Orphan Technologies. HCU Network Australia has received sponsorship from Orphan Technologies and support from the Recordati Rare Disease Foundation,\u00a0Orphan Europe,\u00a0Recordati Rare Diseases Australia,\u00a0Nutricia Metabolics, PIAM,\u00a0BioElectron,\u00a0Vitaflo,\u00a0MetaX,\u00a0Erytech,\u00a0Recordati Rare Diseases\u00a0Brasil and\u00a0CMW SA\u00daDE\u00a0for patient expert meetings.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"124"}}