The prenatal diagnosis of X-linked adrenoleukodystrophy

Moser, Ann B.; Moser, Hugo W.

doi:10.1002/(sici)1097-0223(199901)19:1<46::aid-pd501>3.0.co;2-e

Cited by 40 publications

(21 citation statements)

References 10 publications

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“…Clinically, the disease can manifest very heterogenously with two main phenotypes: the cerebral demyelinating form and adrenomyeloneuropathy (2,3). In contrast to the huge phenotypic variation observed in X-ALD patients, the accumulation of straight-chain very long-chain fatty acids (VLCFAs; carbon backbone of more than 22 carbon atoms) in tissues and plasma as well as in primary fibroblasts is common to all X-ALD patients and therefore used as diagnostic marker (4,5).…”

Section: X-linked Adrenoleukodystrophy (X-ald)mentioning

confidence: 99%

Impaired Very Long-chain Acyl-CoA β-Oxidation in Human X-linked Adrenoleukodystrophy Fibroblasts Is a Direct Consequence of ABCD1 Transporter Dysfunction

Wiesinger

Kunze

Regelsberger

et al. 2013

Journal of Biological Chemistry

126

121

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Background: ABCD1 is a peroxisomal ABC transporter whose dysfunction causes X-linked adrenoleukodystrophy (X-ALD). Results: ␤-Oxidation of C26:0 and C22:0 acyl-CoA esters is impaired in X-ALD. ABCD3 accounts for residual ␤-oxidation activity in X-ALD fibroblasts. Conclusion: ABCD1 mediates very long-chain acyl-CoA ester ␤-oxidation without need for additional re-esterification by an acyl-CoA synthetase. Significance: Our study provides proof of deficient acyl-CoA ester ␤-oxidation in X-ALD.

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Section: X-linked Adrenoleukodystrophy (X-ald)mentioning

confidence: 99%

Impaired Very Long-chain Acyl-CoA β-Oxidation in Human X-linked Adrenoleukodystrophy Fibroblasts Is a Direct Consequence of ABCD1 Transporter Dysfunction

Wiesinger

Kunze

Regelsberger

et al. 2013

Journal of Biological Chemistry

126

121

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“…Please return your comments for the attention of the Commissioning Editor at l.tipton@expert-reviews.com available, but not legal in every country [64][65][66]. Given the increasing therapeutic options in X-ALD, newborn screening appears to be a sensible goal.…”

Section: Genetic Counselingmentioning

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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“…Males diagnosed with ALD via the plasma assay have the option of utilizing DNAbased mutation analysis to identify their genetic change. This information is useful for testing other family members and/or prenatal testing (Moser and Borel 1995;Gartner et al 1997;Moser and Moser 1999;Moser et al 2001;Coll et al 2005).…”

Section: Diagnosismentioning

confidence: 99%

“…Costakos et al (1991) surveyed the attitudes of 136 families affected by ALD towards prenatal, presymptomatic, and carrier testing based on the promise of an impending therapy (Lorenzo's oil), and found that 20.2% of families would hypothetically continue a pregnancy with an affected male if an effective therapy were available. In contrast, the Kennedy Krieger Institute identified 63 affected males prenatally from 1982-1998 and only 5 (8%) of those families decided to continue the pregnancy (Moser and Moser 1999). Availability of adrenal-insufficiency medication, Lorenzo's oil, and bone marrow transplantation may have changed the attitudes of many families toward ALD ).…”

Section: Prenatal Diagnosismentioning

confidence: 99%

Attitudes of Families Affected by Adrenoleukodystrophy toward Prenatal Diagnosis, Presymptomatic and Carrier Testing, and Newborn Screening

et al. 2007

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Families affected by adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) were surveyed to elicit attitudes toward prenatal, presymptomatic and carrier testing, and newborn screening in order to determine the level of support that these families have for current and future genetic testing protocols. Identifying attitudes toward genetic testing, including newborn screening, is especially important because of new data regarding therapeutic options and the possible addition of ALD to newborn screening regimens. The Kennedy Krieger Institute (KKI) database identified 327 prospective participants. Families that were willing to participate in the study received an anonymous questionnaire for completion. Frequencies were generated using SPSS software for Windows. Questionnaires were returned from 128 families for a response rate of 39%. Sons who were at risk for inheriting the ALD gene would be tested by 93% of respondents, and 89.3% would ideally have this testing performed prenatally or in the newborn period. Eighty-nine percent would test an at-risk daughter and 51.2% would ideally have this testing performed prenatally or shortly after birth. ALD newborn screening for males and females was supported by 90% of respondents. If newborn screening for ALD/AMN commences, or there is a new diagnosis of ALD, genetic professionals need to be prepared to have extensive conversations with families regarding the benefits and limitations of current therapeutic and genetic testing options.

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The prenatal diagnosis of X-linked adrenoleukodystrophy

Cited by 40 publications

References 10 publications

Impaired Very Long-chain Acyl-CoA β-Oxidation in Human X-linked Adrenoleukodystrophy Fibroblasts Is a Direct Consequence of ABCD1 Transporter Dysfunction

Impaired Very Long-chain Acyl-CoA β-Oxidation in Human X-linked Adrenoleukodystrophy Fibroblasts Is a Direct Consequence of ABCD1 Transporter Dysfunction

Therapy of X-linked adrenoleukodystrophy

Attitudes of Families Affected by Adrenoleukodystrophy toward Prenatal Diagnosis, Presymptomatic and Carrier Testing, and Newborn Screening

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