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Bladder and Bowel Dysfunction Is Common in Both Men and Women with Mutation of the ABCD1 Gene for X-Linked Adrenoleukodystrophy.

ABSTRACT: BACKGROUND:X-linked adrenoleukodystrophy (X-ALD) is a disorder caused by mutations in the ABCD1 gene. The commonest phenotype of X-ALD is adrenomyeloneuropathy (AMN), which is characterised by involvement of the spinal cord and peripheral nerves. The aim of this study was to evaluate bladder and bowel symptoms in men with AMN and female X-ALD carriers. METHODS:In this cross-sectional study, patients with confirmed mutation of the ABCD1 gene attending a tertiary care service were approached about bladder and bowel complaints and completed the Urinary Symptom Profile (USP), Qualiveen Short Form (SF-Qualiveen), International Prostate Symptom Score (IPSS) and Neurogenic Bowel Dysfunction (NBD) questionnaires. Neurological disability was assessed using the Expanded Disability Status Scale (EDSS). RESULTS:Forty-eight patients participated, 19 males (mean EDSS score (n?=?16) 5.0 (95% CI?±?1.03)) and 29 females (mean EDSS score (n?=?25) 3.2 (95% CI?±?0.98)). Overactive bladder (OAB) symptoms were reported in both males (100%, n?=?19) and females (86.2%, n?=?25). There was no significant gender difference in severity of OAB symptoms (P?=?0.35) and impact on quality of life (P?=?0.13). Furthermore, there was no significant difference in OAB severity when symptoms were compared between female carriers and a cohort of women (n?=?17) with spinal cord damage due to multiple sclerosis (P?=?0.27). Twenty-one percent (n?=?4) of males and 10% (n?=?3) of females had moderate to severe bowel dysfunction. CONCLUSIONS:Bladder and bowel complaints are common in both men with AMN and female carriers. They have a significant impact on the quality of life yet are under-reported and under-treated. Though having an X-linked pattern of inheritance, female carriers may experience overactive bladder symptoms which are as severe as in male patients and are likely to be neurological in origin.

SUBMITTER: Hofereiter J

PROVIDER: S-EPMC4486267 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Bladder and Bowel Dysfunction Is Common in Both Men and Women with Mutation of the ABCD1 Gene for X-Linked Adrenoleukodystrophy.

Hofereiter Johann J Smith Matthew D MD Seth Jai J Tudor Katarina Ivana KI Fox Zoe Z Emmanuel Anton A Murphy Elaine E Lachmann Robin H RH Panicker Jalesh J

JIMD reports 20150313

<h4>Background</h4>X-linked adrenoleukodystrophy (X-ALD) is a disorder caused by mutations in the ABCD1 gene. The commonest phenotype of X-ALD is adrenomyeloneuropathy (AMN), which is characterised by involvement of the spinal cord and peripheral nerves. The aim of this study was to evaluate bladder and bowel symptoms in men with AMN and female X-ALD carriers.<h4>Methods</h4>In this cross-sectional study, patients with confirmed mutation of the ABCD1 gene attending a tertiary care service were a ...[more]

PMID: 25763509

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Project description:X-linked Adrenoleukodystrophy (X-ALD), an inherited peroxisomal metabolic neurodegenerative disorder, is caused by mutations/deletions in the ATP-binding cassette transporter (ABCD1) gene encoding peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). Metabolic dysfunction in X-ALD is characterized by the accumulation of very long chain fatty acids ? C22:0) in the tissues and plasma of patients. Here, we investigated the mitochondrial status following deletion of ABCD1 in B12 oligodendrocytes and U87 astrocytes. This study provides evidence that silencing of peroxisomal protein ABCD1 produces structural and functional perturbations in mitochondria. Activities of electron transport chain-related enzymes and of citric acid cycle (TCA cycle) were reduced; mitochondrial redox status was dysregulated and the mitochondrial membrane potential was disrupted following ABCD1 silencing. A greater reduction in ATP levels and citrate synthase activities was observed in oligodendrocytes as compared to astrocytes. Furthermore, most of the mitochondrial perturbations induced by ABCD1 silencing were corrected by treating cells with suberoylanilide hydroxamic acid, an Histone deacetylase inhibitor. These observations indicate a novel relationship between peroxisomes and mitochondria in cellular homeostasis and the importance of intact peroxisomes in relation to mitochondrial integrity and function in the cell types that participate in the pathobiology of X-ALD. These observations suggest suberoylanilide hydroxamic acid as a potential therapy for X-ALD. Schematic description of the effects of loss of peroxisomal ATP-binding cassette transporter D1 (ABCD1) gene on cellular Redox and mitochondrial activities and their correction by suberoylanilide hydroxamic acid (SAHA) treatment. Pathogenomic accumulation of very long chain fatty acids (VLCFA) as a result of loss of ABCD1 leads to dysfunctions of mitochondrial biogenesis and its activities. Treatment with SAHA corrects mitochondrial dysfunctions. These studies describe unique cooperation between mitochondria and peroxisome for cellular activities.

Dataset Information

Bladder and Bowel Dysfunction Is Common in Both Men and Women with Mutation of the ABCD1 Gene for X-Linked Adrenoleukodystrophy.

Publications

Bladder and Bowel Dysfunction Is Common in Both Men and Women with Mutation of the ABCD1 Gene for X-Linked Adrenoleukodystrophy.

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