Clinical variation in X-linked adrenoleukodystrophy: Fatty acid and lipid metabolism in cultured fibroblasts

Boles, Debra J.; Craft, Debra A.; Padgett, David A.; Loria, Roger M.; Rizzo, William B.

doi:10.1016/0885-4505(91)90010-i

Cited by 29 publications

(14 citation statements)

References 32 publications

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“…Moreover, accumulation of C20:0, C20:1 9, C22:1 9, and C24:1 9 has been noticed in Zellweger fibroblasts (3) but not in X-ALD fibroblasts. This indicates that 9-monounsaturated VLCFA catabolism requires functional peroxisomes but is independent of Abcd1, at least in fibroblasts (3,6). In conclusion, our observations underline the role of peroxisomes in the degradation of saturated and 9-monounsaturated LCFAs and VLCFAs and uncover specific functions for Abcd2, distinct from its overlapping function with Abcd1.…”

Section: Discussionmentioning

confidence: 95%

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Fourcade¹,

Ruíz²,

Camps³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionmentioning

confidence: 95%

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Fourcade¹,

Ruíz²,

Camps³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…Boles and colleagues 30 had shown previously that cultured skin fibroblasts from patients with these two phenotypes had identical VLCFA levels and an identical capacity to metabolize VLCFAs. It has also been shown repeatedly that there is no correlation between X-ALD phenotype and the nature of the mutation.…”

Section: Identification Of Heterozygotesmentioning

confidence: 97%

“…These data are consonant with results in cultured skin fibroblasts reported previously by Boles and associates. 30 Plasma VLCFA Levels in Women Heterozygous for X-ALD Figure 4A through C compare VLCFA levels in 281 women who are obligate heterozygotes for X-ALD, identified as described above, with those levels in 11,814 women who did not have peroxisomal disorders. Univariate ANOVAs indicated that the two groups varied significantly for each of the variables at the 0.0001 level.…”

Section: Fig 2 Density Plots Of Plasma Very Long Chain Fatty Acid (Vmentioning

confidence: 99%

Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls

et al. 1999

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The assay of plasma very long chain fatty acids (VLCFAs), developed in our laboratory in 1981, has become the most widely used procedure for the diagnosis of X‐linked adrenoleukodystrophy (X‐ALD) and other peroxisomal disorders. We present here our 17 years' experience with this assay. Three VLCFA parameters, the level of hexacosanoic acid (C26:0), the ratio of C26:0 to tetracosanoic acid (C24:0), and of C26:0 to docosanoic acid (C22:0), were measured in 1,097 males (hemizygotes) with X‐ALD, 1,282 women heterozygous for this disorder, including 379 obligate heterozygotes, 797 patients with other peroxisomal disorders, and 29,600 control subjects. All X‐ALD hemizygotes who had not previously received Lorenzo's oil or a diet with a high erucic acid content had increased VLCFA levels, but the application of a discriminant function based on all three measurements is required to avoid the serious consequences of a false‐negative result. VLCFA levels are increased at day of birth, thus providing the potential for neonatal mass screening, are identical in the childhood and adult forms, and do not change with age. Eighty‐five percent of obligate heterozygotes had abnormally high VLCFA levels, but a normal result does not exclude carrier status. VLCFA levels were increased in all patients homozygous for Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease, and in patients with deficiencies of peroxisomal acyl‐coenzyme A oxidase, bifunctional enzyme, and 3‐oxoacyl‐coenzyme A thiolase. In these patients the degree of VLCFA excess correlated with clinical severity. Ann Neurol 1999;45:100–110

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“…It is not due to the nature of the mutation [10] or the severity of the defect in very-long-chain fatty oxidation. [11] A Chinese study of 89 patients concluded that the clinical phenotype had no definite relationship with the nature of gene mutation. A single mutation may result in different phenotypes, missense mutation being the most common.…”

Section: Discussionmentioning

confidence: 99%

Intra familial phenotypical variations in adrenoleukodystrophy

Gosalakkal

Balky

2010

Neurol India

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Adrenoleukodystrophy (ALD) is an X-linked recessively inherited peroxisomal disorder, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. It has a wide phenotypical variability ranging from symptomatic childhood cerebral form to the asymptomatic with biochemical defects only; sometimes within the same family. We report a family of three siblings diagnosed with ALD confirmed with the mutations in ABCD1 gene having phenotypical variability ranging from pure adrenal insufficiency to progressive neurodegeneration in the same family. The mother was identified as the carrier and maternal uncle was diagnosed with Adrenomyeloneuropathy. We discuss the variable presentation in our family and the possible causes of phenotypical variability.

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Clinical variation in X-linked adrenoleukodystrophy: Fatty acid and lipid metabolism in cultured fibroblasts

Cited by 29 publications

References 32 publications

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls

Intra familial phenotypical variations in adrenoleukodystrophy

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