{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:19:22Z","timestamp":1781212762169,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T00:00:00Z","timestamp":1275868800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Forty-eight Fabry patients (15 male, 30 treated with enzyme replacement therapy) and 48 sex- and age-matched controls completed a questionnaire on autonomic symptoms (the Autonomic Symptom Profile). Thirty-six Fabry patients underwent cardiovascular function tests.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The Autonomic Symptom Profile revealed a significantly higher sum score in Fabry patients than in healthy control subjects (22 versus 12), but a relatively low score compared to patients with proven autonomic neuropathy. Fabry patients scored worse than healthy controls in the orthostatic intolerance domain. Scores in the male sexual dysfunction domain were comparable between healthy controls and male Fabry patients. The cardiovascular autonomic function tests revealed only mild abnormalities in seven patients. None of these seven patients showed more than one abnormal test result. Enzyme replacement therapy was not associated with less severe disease, lower ASP scores or less frequent abnormal cardiovascular function test results.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Male sexual function and autonomic control of the cardiovascular system are nearly normal in Fabry patients, which cast doubt on the general accepted assumption that autonomic neuropathy is the main cause of symptoms and signs compatible with autonomic dysfunction in Fabry disease. Possibly, end-organ damage plays a key role in the development of symptoms and signs in Fabry patients. An exceptional kind of autonomic neuropathy is another but less likely explanation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2377-10-38","type":"journal-article","created":{"date-parts":[[2010,6,25]],"date-time":"2010-06-25T18:15:22Z","timestamp":1277489722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests"],"prefix":"10.1186","volume":"10","author":[{"given":"Marieke","family":"Biegstraaten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo N","family":"van Schaik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Wieling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits A","family":"Wijburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla EM","family":"Hollak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,6,7]]},"reference":[{"key":"319_CR1","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/mus.10236","volume":"26","author":"CA Luciano","year":"2002","unstructured":"Luciano CA, Russell JW, Banerjee TK, Quirk JM, Scott LJ, Dambrosia JM, et al: Physiological characterization of neuropathy in Fabry's disease. Muscle Nerve. 2002, 26: 622-629. 10.1002\/mus.10236.","journal-title":"Muscle Nerve"},{"key":"319_CR2","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1212\/WNL.52.6.1249","volume":"52","author":"LJC Scott","year":"1999","unstructured":"Scott LJC, Griffin JW, Luciano C, Barton NW, Banerjee T, Crawford T, et al: Quantitative analysis of epidermal innervation in Fabry disease. Neurology. 1999, 52: 1249-1254.","journal-title":"Neurology"},{"key":"319_CR3","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1001\/archneur.1963.00460100061007","volume":"9","author":"AN Rahman","year":"1963","unstructured":"Rahman AN, Lindenberg R: The neuropathology of hereditary dystopic lipidosis. Arch Neurol. 1963, 9: 373-385.","journal-title":"Arch Neurol"},{"key":"319_CR4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1651-2227.2002.tb03108.x","volume":"439","author":"MJ Hilz","year":"2002","unstructured":"Hilz MJ: Evaluation of peripheral and autonomic nerve function in Fabry disease. Acta Paediatr Suppl. 2002, 439: 38-42. 10.1080\/080352502762457905.","journal-title":"Acta Paediatr Suppl"},{"key":"319_CR5","doi-asserted-by":"crossref","first-page":"S150","DOI":"10.1097\/01.ASN.0000015239.57436.18","volume":"13","author":"EH Kolodny","year":"2002","unstructured":"Kolodny EH, Pastores GM: Anderson-Fabry disease: extrarenal, neurological manifestations. J Am Soc Nephrol. 2002, 13: S150-S153.","journal-title":"J Am Soc Nephrol"},{"key":"319_CR6","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1212\/WNL.32.5.498","volume":"32","author":"WJ Cable","year":"1982","unstructured":"Cable WJ, Kolodny EH, Adams RD: Fabry disease: impaired autonomic function. Neurology. 1982, 32: 498-502.","journal-title":"Neurology"},{"key":"319_CR7","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1002\/mus.10497","volume":"28","author":"R Schiffmann","year":"2003","unstructured":"Schiffmann R, Floeter MK, Dambrosia JM, Gupta S, Moore DF, Sharabi Y, et al: Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve. 2003, 28: 703-710. 10.1002\/mus.10497.","journal-title":"Muscle Nerve"},{"key":"319_CR8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.ncl.2007.01.001","volume":"25","author":"R Freeman","year":"2007","unstructured":"Freeman R: Autonomic peripheral neuropathy. Neurol Clin. 2007, 25: 277-301. 10.1016\/j.ncl.2007.01.001.","journal-title":"Neurol Clin"},{"key":"319_CR9","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1080\/08035250500275022","volume":"95","author":"U Ramaswami","year":"2006","unstructured":"Ramaswami U, Whybra C, Parini R, Pintos-Morell G, Mehta A, Sunder-Plassmann G, et al: Clinical manifestations of Fabry disease in children: Data from the Fabry Outcome Survey. Acta Paediatr. 2006, 95: 86-92. 10.1080\/08035250500275022.","journal-title":"Acta Paediatr"},{"key":"319_CR10","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/j.1651-2227.2008.00700.x","volume":"97","author":"C Kampmann","year":"2008","unstructured":"Kampmann C, Wiethoff CM, Whybra CM, Baehner FA, Mengel E, Beck M: Cardiac manifestations of Anderson-Fabry disease in children and adolescents. Acta Paediatr. 2008, 97: 463-469. 10.1111\/j.1651-2227.2008.00700.x.","journal-title":"Acta Paediatr"},{"key":"319_CR11","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1542\/peds.2005-2895","volume":"118","author":"M Ries","year":"2006","unstructured":"Ries M, Clarke JTR, Whybra C, Timmons M, Robinson C, Schlaggar BL, et al: Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics. 2006, 118: 924-932. 10.1542\/peds.2005-2895.","journal-title":"Pediatrics"},{"key":"319_CR12","first-page":"491","volume":"75","author":"SH Morgan","year":"1990","unstructured":"Morgan SH, Rudge P, Smith SJM, Bronstein AM, Kendall BE, Holly E, et al: The neurological complications of Anderson-Fabry disease (alpha-galactosidase A deficiency)--investigation of symptomatic and presymptomatic patients. Q J Med. 1990, 75: 491-507.","journal-title":"Q J Med"},{"key":"319_CR13","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1111\/j.1399-0004.2004.00219.x","volume":"65","author":"C Whybra","year":"2004","unstructured":"Whybra C, Kampmann C, Krummenauer F, Ries M, Mengel E, Miebach E, et al: The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Clin Genet. 2004, 65: 299-307. 10.1111\/j.1399-0004.2004.00219.x.","journal-title":"Clin Genet"},{"key":"319_CR14","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1080\/08035320600618825","volume":"95","author":"M Beck","year":"2006","unstructured":"Beck M: The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease. Acta Paediatr Suppl. 2006, 95: 43-46. 10.1080\/08035320600618825.","journal-title":"Acta Paediatr Suppl"},{"key":"319_CR15","first-page":"315","volume-title":"Textbook of pain","author":"RH Gracely","year":"1994","unstructured":"Gracely RH: Studies of pain in normal man. Textbook of pain. Edited by: Wall PD, Melzack R. 1994, 315-336."},{"key":"319_CR16","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1212\/WNL.52.3.523","volume":"52","author":"GA Suarez","year":"1999","unstructured":"Suarez GA, Opfer-Gehrking TL, Offord KP, Atkinson EJ, O'Brien PC, Low PA: The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms. Neurology. 1999, 52: 523-528.","journal-title":"Neurology"},{"key":"319_CR17","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.2337\/diacare.15.8.1095","volume":"15","author":"R Kahn","year":"1992","unstructured":"Kahn R: Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Autonomic nervous system testing. Diabetes Care. 1992, 15: 1095-1103.","journal-title":"Diabetes Care"},{"key":"319_CR18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/BF00283745","volume":"22","author":"W Wieling","year":"1982","unstructured":"Wieling W, van Brederode JF, de Rijk LG, Borst C, Dunning AJ: Reflex control of heart rate in normal subjects in relation to age: a data base for cardiac vagal neuropathy. Diabetologia. 1982, 22: 163-166. 10.1007\/BF00283745.","journal-title":"Diabetologia"},{"key":"319_CR19","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1085-9489.2006.00076.x","volume":"11","author":"AT Moller","year":"2006","unstructured":"Moller AT, Feldt-Rasmussen U, Rasmussen AK, Sommer C, Hasholt L, Bach FW, et al: Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin. J Peripher Nerv Syst. 2006, 11: 119-125. 10.1111\/j.1085-9489.2006.00076.x.","journal-title":"J Peripher Nerv Syst"},{"key":"319_CR20","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1007\/s00415-004-0364-9","volume":"251","author":"MJ Hilz","year":"2004","unstructured":"Hilz MJ, Kolodny EH, Brys M, Stemper B, Haendl T, Marthol H: Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease. J Neurol. 2004, 251: 564-570. 10.1007\/s00415-004-0364-9.","journal-title":"J Neurol"},{"key":"319_CR21","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1161\/01.STR.32.7.1559","volume":"32","author":"G Altarescu","year":"2001","unstructured":"Altarescu G, Moore DF, Pursley R, Campia U, Goldstein S, Bryant M, et al: Enhanced endothelium-dependent vasodilation in Fabry disease. Stroke. 2001, 32: 1559-1562.","journal-title":"Stroke"},{"key":"319_CR22","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-2377-2-4","volume":"2","author":"DF Moore","year":"2002","unstructured":"Moore DF, Altarescu G, Herscovitch P, Schiffmann R: Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease. BMC Neurol. 2002, 2: 4-10.1186\/1471-2377-2-4.","journal-title":"BMC Neurol"},{"key":"319_CR23","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1161\/hs0202.102601","volume":"33","author":"DF Moore","year":"2002","unstructured":"Moore DF, Altarescu G, Ling GSF, Jeffries N, Frei KP, Weibel T, et al: Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke. 2002, 33: 525-531. 10.1161\/hs0202.102601.","journal-title":"Stroke"},{"key":"319_CR24","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0304-3959(98)00227-9","volume":"80","author":"D Bouhassira","year":"1999","unstructured":"Bouhassira D, Attal N, Willer JC, Brasseur L: Painful and painless peripheral sensory neuropathies due to HIV infection: a comparison using quantitative sensory evaluation. Pain. 1999, 80: 265-272. 10.1016\/S0304-3959(98)00227-9.","journal-title":"Pain"},{"key":"319_CR25","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/mus.20689","volume":"35","author":"V Heldestad","year":"2007","unstructured":"Heldestad V, Nordh E: Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy. Muscle Nerve. 2007, 35: 189-195. 10.1002\/mus.20689.","journal-title":"Muscle Nerve"},{"key":"319_CR26","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1093\/brain\/awh180","volume":"127","author":"CT Shun","year":"2004","unstructured":"Shun CT, Wu HP, Hsieh SC, Lin WM, Lin YH, Tai TY, et al: Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments. Brain. 2004, 127: 1593-1605. 10.1093\/brain\/awh180.","journal-title":"Brain"},{"key":"319_CR27","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1371\/journal.pntd.0000212","volume":"2","author":"WH van Brakel","year":"2008","unstructured":"van Brakel WH, Nicholls PG, Wilder-Smith EP, Das L, Barkataki P, Lockwood DN, et al: Early diagnosis of neuropathy in leprosy-comparing diagnostic tests in a large prospective study (the INFIR Cohort Study). PLoS Negl Trop Dis. 2008, 2: 212-10.1371\/journal.pntd.0000212.","journal-title":"PLoS Negl Trop Dis"},{"key":"319_CR28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0022-510X(95)00355-6","volume":"137","author":"AJ McDougall","year":"1996","unstructured":"McDougall AJ, McLeod JG: Autonomic neuropathy, I. Clinical features, investigation, pathophysiology, and treatment. J Neurol Sci. 1996, 137: 79-88. 10.1016\/0022-510X(95)00355-6.","journal-title":"J Neurol Sci"},{"key":"319_CR29","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1093\/brain\/110.3.563","volume":"110","author":"M Donaghy","year":"1987","unstructured":"Donaghy M, Hakin RN, Bamford JM, Garner A, Kirkby GR, Noble BA, et al: Hereditary sensory neuropathy with neurotrophic keratitis. Description of an autosomal recessive disorder with a selective reduction of small myelinated nerve fibres and a discussion of the classification of the hereditary sensory neuropathies. Brain. 1987, 110: 563-583. 10.1093\/brain\/110.3.563.","journal-title":"Brain"},{"key":"319_CR30","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/j.cgh.2007.08.012","volume":"5","author":"B Hoffmann","year":"2007","unstructured":"Hoffmann B, Schwarz M, Mehta A, Keshav S, Fabry Outcome Survey European Investigators: Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy. Clin Gastroenterol Hepatol. 2007, 5: 1447-1453. 10.1016\/j.cgh.2007.08.012.","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-10-38.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2377-10-38\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-10-38","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2377-10-38.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T12:19:10Z","timestamp":1630498750000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/1471-2377-10-38"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,7]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["319"],"URL":"https:\/\/doi.org\/10.1186\/1471-2377-10-38","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,7]]},"assertion":[{"value":"26 November 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"38"}}