X‐linked adrenoleukodystrophy: Biochemical diagnosis and enzyme defect

Wanders, Ronald J. A.; Roermund, C. W. T. van; Lageweg, W.; Jakobs, Bernadette S.; Schutgens, R. B. H.; Nijenhuis, A. A.; Tager, J. M.

doi:10.1007/bf01799620

Cited by 48 publications

(21 citation statements)

References 48 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…His plasma VLCFA levels were within normal limits, whereas those in cultured skin fibroblasts were characteristic of X-ALD. We were sur- 11,814 women who were free of disorders that involve the peroxisome. Note that there is a greater degree of overlap between X-ALD and the controls than in the male population (see Fig 2) and that application of a discriminant function does not eliminate the overlap.…”

Section: Do False-negative Results Occur?mentioning

confidence: 99%

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

et al. 1999

View full text Add to dashboard Cite

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

show abstract

Section: Do False-negative Results Occur?mentioning

confidence: 99%

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

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Other studies demonstrated that treatment with Lorenzo's Oil was ineffective in changing the clinical course of the disease in 15 Italian and 20 American boys with ALD, who already presented neurologic symptoms at diagnosis (Wanders et al, 1992;Moser et al, 1992). In addition, Korenke et al (1995) assessed the results of treatment with the GTO/GTE mixture in 16 patients, 7 of them asymptomatic.…”

Section: Discussionmentioning

confidence: 99%

“…The major accumulated saturated fatty acids are hexacosanoic acid (C 26:0 ) and tetracosanoic acid (C 24:0 ) Korenke et al, 1995). The increased concentrations of these metabolites cause progressive demyelination of white matter in the central nervous system and adrenal insufficiency (Wanders et al, 1992;Ruiz, 1996;Moser, 1997).…”

Section: Introductionmentioning

confidence: 99%

Clinical and biochemical findings in 7 patients with X-linked adrenoleukodystrophy treated with Lorenzo's Oil

et al. 2000

View full text Add to dashboard Cite

X-Linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of the peroxisomal metabolism biochemically characterized by the accumulation of very long chain fatty acids (VLCFA) in tissues and biological fluids. The major accumulated acids are hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0). The disorder is characterized clinically by central and peripheral demyelination and adrenal insufficiency closely related to the accumulation of fatty acids. The incidence of X-ALD is estimated to be 1:25,000 males. At least six phenotypes can be distinguished. The most common phenotypes are childhood cerebral ALD and adrenomyeloneuropathy (AMN). The recommended therapy consists of the use of the glyceroltrioleate/glyceroltrierucate (GTO/GTE) mixture, known as Lorenzo's Oil, combined with a VLCFA-poor diet. There are alternative treatments such as bone marrow transplantation and immunosuppression, as well as the use of lovastatin and sodium phenylacetate. In the present study we report the clinical and biochemical course of 7 male patients with X-ALD treated with Lorenzo's Oil and a VLCFA-restricted diet. Treatment produced 50% reduction in C26:0 and 42.8% reduction in the C26:0/C22:0 ratio. Most patients remained clinically well, although approximately 30% of them presented a rapid clinical deterioration. The results showed a poor biochemical-clinical correlation for treatment, indicating that new therapies for X-ALD are needed in order to obtain a better prognosis for patients.
A adrenoleucodistrofia ligada ao X (X-ALD) é uma desordem hereditária do metabolismo peroxissomal, bioquimicamente caracterizada pelo acúmulo de ácidos graxos de cadeia muito longa (`very long chain fatty acids"- VLCFA) em diferentes tecidos e em fluidos biológicos, sendo os principais ácidos acumulados o hexacosanóico (C26:0) e o tetracosanóico (C24:0). O acúmulo destes ácidos graxos está associado com desmielinização cerebral e insuficiência adrenal. A incidência desta condição é estimada em 1 para 25.000 em homens. Pelo menos seis fenótipos podem ser distinguidos, sendo a adrenoleucodistrofia (ALD) cerebral infantil e a adrenomieloneuropatia (AMN) os mais comuns. O tratamento preconizado consiste na utilização da mistura gliceroltrioleato/gliceroltrierucato (GTO/GTE), conhecida como Óleo de Lorenzo, combinada com dieta pobre em VLCFA. Existem ainda, terapias alternativas como transplante de medula óssea e imunossupressão, além da utilização de lovastatina e fenilacetato de sódio. Neste trabalho fez-se uma avaliação do tratamento com Óleo de Lorenzo associado à dieta restrita em VLCFA de 7 pacientes homens com X-ALD analisando a evolução clínica e bioquímica. Os pacientes apresentaram uma redução média de 50% nos valores de C26:0 e de 42,8% na razão C26:0/C22:0 após o início do tratamento. A maioria dos pacientes permaneceu clinicamente bem e aproximadamente 30% dos pacientes apresentaram uma progressão rápida no curso clínico da doença. Parece não haver uma clara correlação bioquímico-clínica do tratamento. Os resultados nos mostram...

show abstract

“…However, as previously mentioned, more favorable prognosis depends on treatment beginning before neurological symptoms appear (Moser et al, 1994;Moser, 1995;Korenke et al, 1995). In 15 Italian ALD boys and 20 American ALD boys presenting neurological symptoms, Lorenzo's oil therapy failed to change the clinical course of the disease (Wanders et al, 1992;Moser et al, 1992). Korenke et al (1995) studied 16 patients treated with Lorenzo's oil during 19 months.…”

Section: Resultsmentioning

confidence: 99%

“…It should be differentiated clinically and biochemically from neonatal ALD, an autosomal recessive disorder of peroxisome biogenesis in which the function of at least five peroxisomal enzymes is impaired. In X-ALD, a defect in lignoceroyl-CoA ligase causes pathognomonic tissue accumulation of very long chain fatty acids (VLCFA), mainly hexacosanoic (C26:0) and tetracosanoic acids (C24:0) (Wanders et al, 1988(Wanders et al, , 1992Moser, 1993). Fatty acid accumulation seems responsible for adrenal cortex malfunction and nervous system demyelination Wanders et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

X-linked adrenoleukodystrophy: clinical and laboratory findings in 15 Brazilian patients

et al. 2000

View full text Add to dashboard Cite

Adrenoleukodystrophy (X-ALD) is an X-linked recessively inherited peroxisomal disorder, phenotypically heterogeneous, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. We investigated 15 male X-ALD patients varying in age from 7 to 39, diagnosed among 108 suspected patients referred for investigation. Plasma levels of very long chain fatty acids (VLCFA) were measured at our laboratory using gas chromatography (GC). Eleven cases of childhood X-ALD and four cases of adrenomyeloneuropathy (AMN) were diagnosed. Adrenal leukodystrophy insufficiency and limb weakness were the most frequent symptoms, appearing in 12, 8 and 6 of the patients, respectively. Physician awareness of X-ALD seems inadequate to judge by age at diagnosis and lengthy interval between the start of symptoms and diagnosis. This is the first published series of Brazilian patients with X-ALD. We determined signs and symptoms relevant for diagnosis, as early identification seems important for treatment outcome. In addition, diagnosis identifies carriers, who could benefit from genetic counselling and prenatal diagnosis.

show abstract

X‐linked adrenoleukodystrophy: Biochemical diagnosis and enzyme defect

Cited by 48 publications

References 48 publications

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

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

Clinical and biochemical findings in 7 patients with X-linked adrenoleukodystrophy treated with Lorenzo's Oil

X-linked adrenoleukodystrophy: clinical and laboratory findings in 15 Brazilian patients

Contact Info

Product

Resources

About