X-Linked Adrenoleukodystrophy (ALD): A Novel Mutation of the ALD Gene in 6 Members of a Family Presenting with 5 Different Phenotypes

Berger, Johannes; Molzer, Brunhilde; I, Faé; Bernheimer, H.

doi:10.1006/bbrc.1994.2855

Cited by 115 publications

(68 citation statements)

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“…Only one of the 12 women carrying the mutation showed atypical neurological manifestation, with hemiparesis and without MRI abnormalities in the brain or spinal cord, as cited by van der Knaap and Valk (2005). These distinctive phenotypes support the idea that there are other factors that modify the phenotype of X-adrenoleukodystrophy (Smith et al, 1991;Berger et al, 1994;Kok et al, 1995). The phenotypic variability of the disease can, therefore, be largely influenced by genetic and environmental factors (Pan et al, 2005).…”

Section: Discussionsupporting

confidence: 60%

Novel exon nucleotide deletion causes adrenoleukodystrophy in a Brazilian family

Valadares

Trindade²,

Oliveira³

et al. 2011

Genet. Mol. Res.

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Section: Discussionsupporting

confidence: 60%

Novel exon nucleotide deletion causes adrenoleukodystrophy in a Brazilian family

Valadares

Trindade²,

Oliveira³

et al. 2011

Genet. Mol. Res.

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“…The various phenotypes can occur within the same sibship [11,12]. Several phenotypes can be distinguished:…”

Section: X-ald Phenotypesmentioning

confidence: 99%

Therapy of X-linked adrenoleukodystrophy

Semmler

Köhler

Jung

et al. 2008

Expert Review of Neurotherapeutics

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X-linked adrenoleukodystrophy (X-ALD; OMIM #300100) is caused by defects of the ABCD1 gene on chromosome Xq28, resulting in an impairment of peroxisomal beta-oxidation and the accumulation of saturated very long chain fatty acids (VLCFAs). Primary manifestations occur in the CNS, the adrenal cortex and the testes' Leydig cells. The clinical presentation shows a marked variability which is not explained by the different X-ALD genotypes. Phenotypes range from rapidly progressive cerebral disease with childhood (childhood cerebral ALD [CCALD]) or adulthood (adult cerebral ALD [ACALD]) onset leading to death within a few years, over adult-onset adrenomyeloneuropathy (AMN) with or without focal CNS demyelination, AMN converting into a rapidly progressive, cerebral demyelinating phenotype resembling CCALD, to slow disease progression over decades, or adrenal insufficiency only. Approximately 50% of female heterozygotes develop moderate spastic paresis resembling the AMN phenotype. This review focuses on current experiences with different therapeutic approaches. Lorenzo's oil did not prove to be effective in cerebral inflammatory disease variants, but asymptomatic patients, and speculatively AMN variants without cerebral involvement, as well as female carriers may benefit from early intake of oleic and erucic acids in addition to VLCFA restriction. Hormone-replacement therapy is necessary in all patients with adrenal insufficiency. Hematopoietic stem cell transplantation has been reported to be effective in presymptomatic or early symptomatic CCALD, and may well also be a final therapeutic option in early ACALD patients. Early detection of mutation carriers and timely initiation of therapy is important for the effectiveness of all therapeutic efforts. Gene therapy of endogenous hematopoietic stem cells, pharmacological upregulation of other genes encoding proteins involved in peroxisomal beta-oxidation, reduction of oxidative stress, and possibly lovastatin are candidates for future X-ALD therapies. Future Drugs Ltd: Peer Review PaperPlease return your comments for the attention of the Commissioning Editor at l.tipton@expert-reviews.com Many thanks in advance for your kind assistance. Therapy of X-linked Adrenoleukodystrophy Future Drugs Ltd: Peer Review PaperPlease return your comments for the attention of the Commissioning Editor at l.tipton@expert-reviews.com Many thanks in advance for your kind assistance. et al 1963 [6]. In 1981 the X-ALD locus was mapped to chromosome Xq28 [7], and twelve years later, the X-ALD gene (ABCD1) was identified [8,9]. Today X-ALD has been identified in most countries worldwide and in most ethnic groups. The minimum frequency of hemizygotes in the UnitedStates was determined to be 1:42,000 and the one of hemizygotes plus heterozygotes 1:16,800, suggesting X-ALD as the most common inherited leukodystrophy [10]. X-ALD phenotypesX-ALD is characterized by a highly variable clinical spectrum, from early progressive childhood to mild adulthood disease with only slow symptom progre...

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“…7 However, a lack of correlation between genotype and phenotype renders precise prediction of disease in an affected individual impossible, even within familial cohorts. 8 Approximately 80% of ALD patients develop neurologic involvement. Up to 25% of these demonstrate a long axonopathy of the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report

Miller

Rothman

Nascene

et al. 2011

Blood

252

269

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Cerebral adrenoleukodystrophy (cALD) remains a devastating neurodegenerative disease; only allogeneic hematopoietic cell transplantation (HCT) has been shown to provide long-term disease stabilization and survival. Sixty boys undergoing HCT for cALD from 2000 to 2009 were analyzed. The median age at HCT was 8.7 years; conditioning regimens and allograft sources varied. At HCT, 50% demonstrated a Loes radiographic severity score > 10, and 62% showed clinical evidence of neurologic dysfunction. A total of 78% (n ‫؍‬ 47) are alive at a median 3.7 years after HCT. The estimate of 5-year survival for boys with Loes score < 10 at HCT was 89%, whereas that for boys with Loes score > 10 was 60% (P ‫؍‬ .03). The 5-year survival estimate for boys absent of clinical cerebral disease at HCT was 91%, whereas that for boys with neurologic dysfunction was 66% (P ‫؍‬ .08). The cumulative incidence of transplantationrelated mortality at day 100 was 8%. Posttransplantation progression of neurologic dysfunction depended significantly on the pre-HCT Loes score and clinical neurologic status. We describe the largest single-institution analysis of survival and neurologic function outcomes after HCT in cALD. These trials were registered at www.clinicaltrials.gov as #NCT00176904, #NCT00668564, and #NCT00383448. (Blood. 2011;118(7): [1971][1972][1973][1974][1975][1976][1977][1978]

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X-Linked Adrenoleukodystrophy (ALD): A Novel Mutation of the ALD Gene in 6 Members of a Family Presenting with 5 Different Phenotypes

Cited by 115 publications

References 0 publications

Novel exon nucleotide deletion causes adrenoleukodystrophy in a Brazilian family

Novel exon nucleotide deletion causes adrenoleukodystrophy in a Brazilian family

Therapy of X-linked adrenoleukodystrophy

Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report

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