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Cited by 19Urinary Bladder and Prostate ResearchMetabolism and Genetic DisordersLysosomal Storage Disorders Research

Beyond gait and balance: Urinary and bowel dysfunction in X-linked adrenoleukodystrophy

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Corre, Camille S., Grant, Natalie, Sadjadi, Reza, Hayden, Douglas, Becker, Catherine, Gomery, Pablo, Eichler, Florian S.·2021·Orphanet Journal of Rare Diseases
DOI 10.1186/s13023-020-01596-1PMC PMC7789359
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Abstract

Objective: 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. Methods: In this retrospective and prospective study, we performed medical record review (n = 103), analyzed the results of clinically indicated urodynamic testing (n = 11), and developed and distributed a symptom and quality of life (QOL) survey (n = 59). Results: 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. Conclusions: 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.

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  • The majority of women with ALD are not merely carriers but may develop some degree of myeloneuropathy leading to gait, bowel, and bladder dysfunction.

    “It is becoming increasingly recognized that the majority of women are not merely carriers, but may develop some degree of myeloneuropathy leading to gait, bowel, and bladder dysfunction [14,15,63].”

    From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [63]

    The Results (Study population; Cross-sectional symptom prevalence and age of onset) report neurological signs or symptoms in 91.5% of females in the cohort, urinary symptoms in 78.8%, and bowel symptoms in 67.3%. This supports the point that women with ALD can be symptomatic rather than merely carriers. The Discussion cautions that a cohort largely drawn from patients seeking neurological evaluation may overestimate prevalence in the broader ALD population, so the paper does not establish that the majority of all women with ALD develop this combination of problems. (LLM, conf=0.84)

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  • AMN is characterized by loss of sensation in the legs followed by a spastic gait with positive Babinski reflex, progressing inexorably, associated with ataxia, leg pain, impotence, and voiding abnormalities.

    “Loss of sensation in the legs is followed by a spastic gait with positive Babinski reflex, which progresses inexorably, associated with ataxia, leg pain, impotence, and voiding abnormalities [49,50,51,52].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [50]

    The Background and Discussion (page not provided) describe AMN as involving sensory impairment, a slowly progressive spastic gait disorder, sensory ataxia, and bladder dysfunction. They do not establish that leg sensory loss precedes gait changes or report a positive Babinski reflex, leg pain, or impotence. The Results (Cross-sectional symptom prevalence and age of onset; page not provided) instead report that urinary or bowel symptoms preceded other myelopathy symptoms in 57.8% of symptomatic patients. (LLM, conf=0.88)

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Research works printed but not linked: 21

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Sorted by citations

Authors
Corre, C. S., Grant, N., Sadjadi, R., Hayden, D., Becker, C., Gomery, P., & Eichler, F. S.
Affiliations
  • Massachusetts General Hospital (US)
  • Harvard University (US)
Corresponding author
Eichler, Florian S.
ORCID
Venue
Orphanet Journal of Rare Diseases
Publisher
Springer Science and Business Media LLC
Published
2021-01-06
Volume
16
Issue
1
Pages
14-14
ISSN
1750-1172 (ISSN-L)
DOI
10.1186/s13023-020-01596-1
PMC
PMC7789359
OpenAlex
W3120162919
Cited by
19
References
4
Citations by year
2025: 5 · 2024: 8 · 2023: 4 · 2022: 2
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Massachusetts General Hospital
Topics
  • Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
X-linked adrenoleukodystrophy, urinary dysfunction, bowel dysfunction, neurogenic bladder, urinary urgency, urinary incontinence, urodynamics, detrusor contraction, sphincter relaxation, quality of life, sex differences, symptom onset, adults
MeSH terms
Adrenoleukodystrophy, Adult, Female, Gait, Humans, Male, Prospective Studies, Quality of Life, Retrospective Studies, Urinary Tract

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