{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T02:20:09Z","timestamp":1766197209204,"version":"3.37.3"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Objective<\/jats:title>\n                <jats:p>To characterize the prevalence, onset, and burden of urinary and bowel dysfunction in adult patients with adrenoleukodystrophy (ALD) and to evaluate any sex differences in symptom presentation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this retrospective and prospective study, we performed medical record review (n\u2009=\u2009103), analyzed the results of clinically indicated urodynamic testing (n\u2009=\u200911), and developed and distributed a symptom and quality of life (QOL) survey (n\u2009=\u200959).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Urinary and bowel symptoms are highly prevalent in both males (75.0%) and females (78.8%) in this population, most commonly urinary urgency, often leading to incontinence. Time to onset of first urinary or bowel symptom occurs approximately a decade earlier in males. Seventy-two percent of symptomatic patients report a limitation to QOL. Urodynamic evaluation provides evidence of three distinct mechanisms underlying lower urinary tract dysfunction: involuntary detrusor contractions (indicating uncontrolled neuronal stimulation with or without leakage), motor underactivity of the bladder, and asynergy between detrusor contraction and sphincter relaxation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Beyond gait and balance difficulties, urinary and bowel symptoms are common in adults with ALD and impair QOL. Males are affected at a younger age but both sexes experience a higher symptom burden with age. As this population also experiences gait and balance impairment, patients with ALD are more vulnerable to urinary urgency leading to incontinence. Urodynamic evaluation may help better elucidate the pathophysiologic mechanisms underlying neurogenic lower urinary tract dysfunction, which can allow more targeted treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-020-01596-1","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T19:04:06Z","timestamp":1609959846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Beyond gait and balance: urinary and bowel dysfunction in X-linked adrenoleukodystrophy"],"prefix":"10.1186","volume":"16","author":[{"given":"Camille S.","family":"Corre","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Grant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Sadjadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Hayden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Gomery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-1089","authenticated-orcid":false,"given":"Florian S.","family":"Eichler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"issue":"10","key":"1596_CR1","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1212\/WNL.31.10.1241","volume":"31","author":"HW Moser","year":"1981","unstructured":"Moser HW, Moser AB, Frayer KK, et al. Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology. 1981;31(10):1241\u20139.","journal-title":"Neurology"},{"issue":"9","key":"1596_CR2","first-page":"1465","volume":"1822","author":"S Kemp","year":"2012","unstructured":"Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: clinical, metabolic, genetic, and pathophysiological aspects. BiochimBiophysActa. 2012;1822(9):1465\u201374.","journal-title":"BiochimBiophysActa"},{"key":"1596_CR3","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1750-1172-7-51","volume":"7","author":"M Engelen","year":"2012","unstructured":"Engelen M, Kemp S, de Visser M, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7:51.","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"1596_CR4","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1046\/j.1442-2042.2001.00271.x","volume":"8","author":"H Shinbo","year":"2001","unstructured":"Shinbo H, Kageyama S, Hayami S, et al. Voiding dysfunction in a patient with adolescent adrenoleukodystrophy. Int J Urol. 2001;8(3):144\u20137.","journal-title":"Int J Urol"},{"issue":"4","key":"1596_CR5","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1007\/BF01367665","volume":"15","author":"MM Walther","year":"1997","unstructured":"Walther MM, Cutler GB. Urodynamic abnormalities in two brothers with adrenomyeloneuropathy. World J Urol. 1997;15(4):262\u20135.","journal-title":"World J Urol"},{"issue":"3","key":"1596_CR6","first-page":"207","volume":"17","author":"R Sakakibara","year":"1998","unstructured":"Sakakibara R, Hattori T, Fukutake T, Mori M, Yamanishi T, Yasuda K. Micturitional disturbance in a patient with adrenomyeloneuropathy (AMN). NeurourolUrodyn. 1998;17(3):207\u201312.","journal-title":"NeurourolUrodyn"},{"issue":"2","key":"1596_CR7","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1212\/WNL.31.2.151","volume":"31","author":"BP O\u2019Neill","year":"1981","unstructured":"O\u2019Neill BP, Mannion LC, Feringa ER. Theadrenoleukomyeloneuropathy complex: expression in four generations. Neurology. 1981;31(2):151\u20136.","journal-title":"Neurology"},{"key":"1596_CR8","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1212\/WNL.27.12.1107","volume":"27","author":"JW Griffin","year":"1977","unstructured":"Griffin JW, Goren E, Schaumburg H, Engel WK, Loriaux L. Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. Neurology. 1977;27:1107\u201313.","journal-title":"Neurology"},{"issue":"6 Pt 2","key":"1596_CR9","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1097\/01.ju.0000110885.26017.b0","volume":"171","author":"M Silveri","year":"2004","unstructured":"Silveri M, De Gennaro M, Gatti C, Bizzarri C, Mosiello G, Cappa M. Voiding dysfunction in x-linked adrenoleukodystrophy: symptom score and urodynamic findings. J Urol. 2004;171(6 Pt 2):2651\u20133.","journal-title":"J Urol"},{"issue":"4","key":"1596_CR10","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/brain\/awx016","volume":"140","author":"J-S K\u00fchl","year":"2017","unstructured":"K\u00fchl J-S, Suarez F, Gillett GT, et al. Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy. Brain. 2017;140(4):953\u201366.","journal-title":"Brain"},{"issue":"3","key":"1596_CR11","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1093\/brain\/awt361","volume":"137","author":"M Engelen","year":"2014","unstructured":"Engelen M, Barbier M, Dijkstra IM, et al. X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain. 2014;137(3):693\u2013706.","journal-title":"Brain"},{"key":"1596_CR12","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/8904_2015_414","volume":"22","author":"J Hofereiter","year":"2015","unstructured":"Hofereiter J, Smith MD, Seth J, et al. Bladder and bowel dysfunction is common in both men and women with mutation of the ABCD1 gene for x-linked adrenoleukodystrophy. JIMD Rep. 2015;22:77\u201383.","journal-title":"JIMD Rep"},{"key":"1596_CR13","unstructured":"Haylen B. (ed.) ICS glossary of terminology. https:\/\/www.ics.org\/glossary. Accessed 21 April 2020."},{"issue":"1","key":"1596_CR14","first-page":"1","volume":"16","author":"D Griffiths","year":"1997","unstructured":"Griffiths D, H\u00f6fner K, van Mastrigt R, Rollema HJ, Sp\u00e5ngberg A, Gleason D. Standardization of terminology of lower urinary tract function: pressure-flow studies of voiding, urethral resistance, and urethral obstruction. NeurourolUrodyn. 1997;16(1):1\u201318.","journal-title":"NeurourolUrodyn"},{"issue":"6","key":"1596_CR15","first-page":"14","volume":"7","author":"VW Nitti","year":"2005","unstructured":"Nitti VW. Pressure flow urodynamics: the gold standard for diagnosing bladder outlet obstruction. Rev Urol. 2005;7(6):14\u201321.","journal-title":"Rev Urol"},{"key":"1596_CR16","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1080\/01621459.1997.10474049","volume":"92","author":"JA Wellner","year":"1997","unstructured":"Wellner JA, Zhan Y. A hybrid algorithm for computation of the nonparametric maximum likelihood estimator from censored data. J Am Stat Assoc. 1997;92:945\u201359.","journal-title":"J Am Stat Assoc"},{"key":"1596_CR17","unstructured":"Guo C, So Y, Johnston G. Analyzing interval-censored data with ICLIFETEST procedure. In: SAS Institute Inc, 2014. https:\/\/support.sas.com\/resources\/papers\/proceedings14\/SAS279-2014.pdf. Accessed 21 April 2020."},{"issue":"2","key":"1596_CR18","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1093\/brain\/awy299","volume":"142","author":"IC Huffnagel","year":"2019","unstructured":"Huffnagel IC, van Ballegoij WJC, van Geel BM, Vos JMBW, Kemp S, Engelen M. Progression of myelopathy in males with adrenoleukodystrophy: towards clinical trial readiness. Brain. 2019;142(2):334\u201343.","journal-title":"Brain"},{"issue":"1","key":"1596_CR19","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s13023-017-0709-y","volume":"12","author":"M Lad","year":"2017","unstructured":"Lad M, Parkinson MH, Rai M, et al. Urinary, bowel and sexual symptoms in a cohort of patients with Friedreich\u2019s ataxia. Orphanet J Rare Dis. 2017;12(1):158.","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"1596_CR20","first-page":"263","volume":"81","author":"M Braschinsky","year":"2010","unstructured":"Braschinsky M, Zopp I, Kals M, Haldre S, Gross-Paju K. Bladder dysfunction in hereditary spastic paraplegia: what to expect? J NeurolNeurosurgPsychiatr. 2010;81(3):263\u20136.","journal-title":"J NeurolNeurosurgPsychiatr"},{"key":"1596_CR21","first-page":"230","volume":"32","author":"KS Coyne","year":"2013","unstructured":"Coyne KS, Sexton CC, Bell JA, et al. The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) by racial\/ethnic group and age: results from OAB-POLL. NeurourolUrodyn. 2013;32:230\u20137.","journal-title":"NeurourolUrodyn"},{"key":"1596_CR22","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1093\/aje\/kwm356","volume":"167","author":"SL Tennstedt","year":"2008","unstructured":"Tennstedt SL, Link CL, Steers WD, McKinlay JB. Prevalence of and risk factors for urine leakage in a racially and ethnically diverse population of adults: The Boston Area Community Health (BACH) survey. Am J Epidemiol. 2008;167:390\u20139.","journal-title":"Am J Epidemiol"},{"issue":"4","key":"1596_CR23","first-page":"636","volume":"12","author":"D Ivo","year":"2014","unstructured":"Ivo D, Devaki P, Luma HN, et al. Prevalence, trends, and risk factors for fecal incontinence in United States Adults, 2005\u20132010. ClinGastroenterolHepatol. 2014;12(4):636\u201343.","journal-title":"ClinGastroenterolHepatol"},{"key":"1596_CR24","first-page":"6","volume":"29","author":"LR Schiller","year":"2014","unstructured":"Schiller LR, Pardi DS, Spiller R, et al. Gastro 2013 APDW\/WCOG Shanghai working party report: chronic diarrhea: definition, classification, diagnosis. J GastroenterolHepatol. 2014;29:6\u201325.","journal-title":"J GastroenterolHepatol"},{"issue":"12","key":"1596_CR25","doi-asserted-by":"publisher","first-page":"3530","DOI":"10.1111\/j.1572-0241.1999.01642.x","volume":"94","author":"WF Stewart","year":"1999","unstructured":"Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol. 1999;94(12):3530\u201340.","journal-title":"Am J Gastroenterol"},{"issue":"12","key":"1596_CR26","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1111\/j.1471-0528.2000.tb11669.x","volume":"107","author":"AH MacLennan","year":"2000","unstructured":"MacLennan AH, Taylor AW, Wilson DH, Wilson D. The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery. BJOG. 2000;107(12):1460\u201370.","journal-title":"BJOG"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-020-01596-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-020-01596-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-020-01596-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T20:14:41Z","timestamp":1609964081000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-020-01596-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,6]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1596"],"URL":"https:\/\/doi.org\/10.1186\/s13023-020-01596-1","relation":{},"ISSN":["1750-1172"],"issn-type":[{"type":"electronic","value":"1750-1172"}],"subject":[],"published":{"date-parts":[[2021,1,6]]},"assertion":[{"value":"3 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the local Institutional Review Board, Partners Human Research Committee (PHRC), prior to patient enrollment and included both a prospective protocol (2017P002437) and a retrospective medical record review protocol (2012P000132). For the retrospective protocol, formal informed consent was waived by the PHRC. For the prospective protocol, return of a completed survey implied consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"FE is the PI of Bluebird Bio and Minoryx Therapeutics clinical trials.\u00a0He is a consultant to Ionis, Alnylam, Sanofi Genzyme, Minoryx, and SwanBio Therapeutics. He is the Director of the Third Rock MGH Neuroscience Fellowship. He is the Founder of SwanBio Therapeutics.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}