Adrenoleukodystrophy: A Clinical, Pathological and Biochemical Study

Schaumburg, Herbert H.; Powers, James M.; Raine, Cedric S.; Johnson, Anne B.; Kolodny, Edwin H.; Kishimoto, Yasuo; Igarashi, Masahiro; Suzuki, Kinuko

doi:10.1007/978-1-4684-7735-1_25

Cited by 94 publications

(129 citation statements)

References 7 publications

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“…The most common type is the childhood form (32) that usually presents between age 4 and 8 years, involves mainly the cerebral white matter and adrenal cortex, and leads to death during the first or second, decade. Pedigree analysis is consistent with X-linked mode of inheritance (32). This has been confirmed by studies with cultured skin fibroblasts and the ALD gene has been mapped to Xq28 (19).…”

Section: Discussionsupporting

confidence: 66%

“…The accumulation of these fatty acids, coupled with the metabolic data presented here, suggests that normal catabolism of very long chain fatty acids involves a metabolic pathway which is distinct from that for other fatty acids, and that this pathway is genetically deficient in patients with ALD. Abbreviations ALD, adrenoleukodystrophy AMN, adrenomyeloneuropathy C22:0, docosanoic acid (behenic acid) C24:0, tetracosanoic acid (lignoceric acid) C26:0, hexacosanoic acid (cerotic acid) C27:0, heptacosanoic acid GLC, gas liquid chromatography WBC, white blood cell ALD is a genetically-determined, progressive disorder which affects mainly the adrenal cortex and the white matter of the nervous system (32). It is associated with the accumulation of saturated very long chain fatty acids (mainly C26:0, C25:0, and C24:O) in the cholesterol esters and gangliosides in these tissues (1 1, 17,30).…”

Section: Discussionmentioning

confidence: 99%

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Adrenoleukodystrophy: Impaired Oxidation of Very Long Chain Fatty Acids in White Blood Cells, Cultured Skin Fibroblasts, and Amniocytes

et al. 1984

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SummaryWe compared the formation of I4CO2 from [I-I4C]fatty acids in homogenates of cultured skin fibroblasts and white blood cells from 25 patients with adrenoleukodystrophy (ALD) and from 24 controls. The ALD group included 16 boys with childhood ALD, five men with adrenomyeloneuropathy (AMN), and two boys and two girls with neonatal ALD. The substrates were unbranched saturated fatty acids ranging in chain length from 16-26 carbons. From C24:0, the radioactive C 0 2 production by homogenates of ALD fibroblasts and white blood cells was 17% and 37% of control, respectively, and from C26:O it was 17% of control in ALD fibroblasts. The C 0 2 evolution from palmitate (C16:O) in the ALD was identical to the control group; for C18:0, the value for ALD cells was 76% of control, and fatty acids with chain lengths between C18:O and C24:O gave intermediate results.Results for childhood ALD patients were similar to those for the AMN patients. More limited studies with cultured amniocytes of fetuses with childhood ALD gave results similar to those obtained with cultured skin fibroblasts, and results with neonatal ALD patients appeared to be the same as for childhood ALD and AMN. Studies of three women who were carriers for childhood ALD gave values intermediate between ALD and control. The total C26:O levels in ALD cultured skin fibroblasts and white blood cells were 4-6 times that of control; the total C24:O levels were increased 10-30%, whereas the C22:O levels were unchanged.The results suggest that ALD patients have a defect in the oxidation of very long chain fatty acids (C24:O and longer) but not for the degradation of fatty acids with a chain length of 18 carbons or less. Such a defect could account for the accumulation of the very long chain fatty acids in a variety of tissues and lipid moieties. The accumulation of these fatty acids, coupled with the metabolic data presented here, suggests that normal catabolism of very long chain fatty acids involves a metabolic pathway which is distinct from that for other fatty acids, and that this pathway is genetically deficient in patients with ALD.Abbreviations ALD, adrenoleukodystrophy AMN, adrenomyeloneuropathy C22:0, docosanoic acid (behenic acid) C24:0, tetracosanoic acid (lignoceric acid) C26:0, hexacosanoic acid (cerotic acid) C27:0, heptacosanoic acid GLC, gas liquid chromatography WBC, white blood cell ALD is a genetically-determined, progressive disorder which affects mainly the adrenal cortex and the white matter of the nervous system (32). It is associated with the accumulation of saturated very long chain fatty acids (mainly C26:0, C25:0, and C24:O) in the cholesterol esters and gangliosides in these tissues (1 1, 17, 30). Accumulation of these same fatty acids has also been reported in sphingomyelin and other lipid moieties of plasma (23) and red blood cells (38) and in cultured skin fibroblasts (22), cultured muscle cells (I), and cultured amniocytes (24).Several types of ALD have been described. The most common type is the childhood form (32) that usually p...

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Adrenoleukodystrophy: Impaired Oxidation of Very Long Chain Fatty Acids in White Blood Cells, Cultured Skin Fibroblasts, and Amniocytes

et al. 1984

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“…Although the exact biochemical changes in white matter that are responsible for PML are not known, the accumulation of long-chain fatty acids in other demyelinating diseases including adrenoleukodystrophy 21,22 and solvent vapor abuse leukoencephalopathy 23 have been described. The accumulations of long-chain sphingomyelins and ceramides that we observed in the CSF of HIV patients with inactive and active dementia may thus reflect ongoing damage to white matter in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Associative and predictive biomarkers of dementia in HIV-1–infected patients

Bandaru

McArthur²,

Sacktor³

et al. 2007

Neurology

110

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Background-Infection with HIV can result in a debilitating CNS disorder known as HIV dementia (HIV-D). Since the advent of highly active antiretroviral therapy (HAART), the incidence of HIV-D has declined, but the prevalence continues to increase. In this new era of HIV-D, traditional biomarkers such as CSF viral load and monocyte chemotactic protein 1 levels are less likely to be associated with dementia in patients on HAART and biomarkers that can predict HIV-D have not yet been identified.

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“…Ito et al 40 investigated ALD with DTI, showing a graded increase in diffusivity and reduction in diffusion anisotropy towards the centre of the MR-visible lesions, which they thought might correspond to the zones found on histology. 41 …”

Section: White Matter Diseases In Childrenmentioning

confidence: 99%

Applications of diffusion‐weighted and diffusion tensor MRI to white matter diseases – a review

2002

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This paper reviews the current applications of diffusion-weighted and diffusion tensor MRI in diseases of the brain white matter. The contribution that diffusion-weighted imaging has made to our understanding of white matter diseases is critically appraised. The quantitative nature of diffusion MRI is one of its major attractions; however, this is offset by the more advanced hardware required to collect diffusion-weighted images reliably, and the more complex processing to produce quantitative parametric diffusion images. With the now common availability of scanners equipped to perform echo-planar imaging, the acquisition of diffusion tensor images is sure to become more widespread and routine.

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Adrenoleukodystrophy: A Clinical, Pathological and Biochemical Study

Cited by 94 publications

References 7 publications

Adrenoleukodystrophy: Impaired Oxidation of Very Long Chain Fatty Acids in White Blood Cells, Cultured Skin Fibroblasts, and Amniocytes

Adrenoleukodystrophy: Impaired Oxidation of Very Long Chain Fatty Acids in White Blood Cells, Cultured Skin Fibroblasts, and Amniocytes

Associative and predictive biomarkers of dementia in HIV-1–infected patients

Applications of diffusion‐weighted and diffusion tensor MRI to white matter diseases – a review

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