Effects of hematopoietic stem cell transplantation on acyl‐CoA oxidase deficiency: a sibling comparison study

Wang, Raymond; Monuki, Edwin S.; Powers, James M.; Schwartz, Phillip H.; Watkins, Paul A.; Shi, Yang; Moser, Ann B.; Shrier, David A.; Waterham, Hans R.; Nugent, Diane J.; Abdenur, José E.

doi:10.1007/s10545-014-9698-3

Cited by 18 publications

(9 citation statements)

References 36 publications

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“…Unfortunately, as far as we know, follow up studies were not published on these patients. Hematopoietic stem cell transplantation was reported for one case of ACOX1 deficiency (neonatal adrenoleukodystrophy), but no information on hepatic parameters was provided and the patient died some years later from pneumonia without improvement in psychomotor development [142].…”

Section: Potential Treatments For Hepatic Peroxisome Pathologiesmentioning

confidence: 99%

Hepatic dysfunction in peroxisomal disorders

Baes

Veldhoven

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The peroxisomal compartment in hepatocytes hosts several essential metabolic conversions. These are defective in peroxisomal disorders that are either caused by failure to import the enzymes in the organelle or by mutations in the enzymes or in transporters needed to transfer the substrates across the peroxisomal membrane. Hepatic pathology is one of the cardinal features in disorders of peroxisome biogenesis and peroxisomal β-oxidation although it only rarely determines the clinical fate. In mouse models of these diseases liver pathologies also occur, although these are not always concordant with the human phenotype which might be due to differences in diet, expression of enzymes and backup mechanisms. Besides the morphological changes, we overview the impact of peroxisome malfunction on other cellular compartments including mitochondria and the ER. We further focus on the metabolic pathways that are affected such as bile acid formation, and dicarboxylic acid and branched chain fatty acid degradation. It appears that the association between deregulated metabolites and pathological events remains unclear.

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Section: Potential Treatments For Hepatic Peroxisome Pathologiesmentioning

confidence: 99%

Hepatic dysfunction in peroxisomal disorders

Baes

Veldhoven

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…In addition to a delay in attaining early developmental milestones, almost all ACOX1-deficient children aged 24 to 48 months showed regression of motor achievements. Brain MRI studies demonstrated myelin loss starting in the white matter of the cerebellum, cerebellar peduncles and brainstem tracts, progressively extending to the midbrain and the cortical white matter (21,80,100,111,125,146,149).…”

Section: Acyl-coa Oxidase-1 Deficiencymentioning

confidence: 99%

Peroxisomal Disorders: A Review on Cerebellar Pathologies

Munter

Verheijden

Régal³

et al. 2015

Brain Pathology

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Peroxisomes are organelles with diverse metabolic tasks including essential roles in lipid metabolism. They are of utmost importance for the normal functioning of the nervous system as most peroxisomal disorders are accompanied with neurological symptoms. Remarkably, the cerebellum exquisitely depends on intact peroxisomal function both during development and adulthood. In this review, we cover all aspects of cerebellar pathology that were reported in peroxisome biogenesis disorders and in diseases caused by dysfunction of the peroxisomal α-oxidation, β-oxidation or ether lipid synthesis pathways. We also discuss the phenotypes of mouse models in which cerebellar pathologies were recapitulated and search for connections with the metabolic abnormalities. It becomes increasingly clear that besides the most severe forms of peroxisome dysfunction that are associated with developmental cerebellar defects, milder impairments can give rise to ataxia later in life.

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“…Recently, it has been recognized that a proportion of patients with acyl‐CoA oxidase deficiency (ACOX1; OMIM 609751) may exhibit similar clinical, radiological and histopathological features to those of X‐ALD, especially in the cerebello‐brainstem form . Inherited deficiencies of peroxisomal straight chain VLCFA β‐oxidation include only X‐ALD and straight‐chain acyl‐CoA oxidase deficiency.…”

Section: Discussionmentioning

confidence: 99%

Adult‐onset cerebello‐brainstem dominant form of X‐linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review

et al. 2015

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X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the differential diagnosis of MSA.

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Effects of hematopoietic stem cell transplantation on acyl‐CoA oxidase deficiency: a sibling comparison study

Cited by 18 publications

References 36 publications

Hepatic dysfunction in peroxisomal disorders

Hepatic dysfunction in peroxisomal disorders

Peroxisomal Disorders: A Review on Cerebellar Pathologies

Adult‐onset cerebello‐brainstem dominant form of X‐linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review

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