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

Camille S Corre,Douglas Hayden,Pablo Gomery,Florian S Eichler,Reza Sadjadi,Natalie Grant,Catherine Becker

doi:10.1186/s13023-020-01596-1

Abstract

ObjectiveTo 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.MethodsIn 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).ResultsUrinary 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.ConclusionsBeyond 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.

Highlights

X-linked adrenoleukodystrophy (ALD) is a single gene disorder caused by mutations in the ABCD1 peroxisomal half-transporter gene, resulting in accumulation of very long chain fatty acids (VLCFAs) [1]
Retrospective medical record review We retrospectively reviewed electronic medical records of all adult patients with ALD seen in the Massachusetts General Hospital (MGH) Leukodystrophy Clinic by F.E. and C.B. between May 2005 and May 2019
Study population We describe a population of 109 adults with ALD, of which 56 (51.4%) were male and 53 (48.6%) were female

Summary

Introduction

X-linked adrenoleukodystrophy (ALD) is a single gene disorder caused by mutations in the ABCD1 peroxisomal half-transporter gene, resulting in accumulation of very long chain fatty acids (VLCFAs) [1]. Beyond a handful of early case reports and case series [4,5,6,7,8,9,10], two prospective studies have described the prevalence of urinary and bowel symptoms across larger cohorts. The first study (n = 46) assessed symptoms in females with ALD, finding both urinary and fecal. Fecal incontinence was reported as an early symptom, even occurring in a few patients without signs of myelopathy on exam. The majority of patients disclosed either no or “very minor” bowel symptoms. As these studies were limited by sex or phenotype, the prevalence and impact of these symptoms across the phenotypic spectrum have not been characterized to date

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