Adrenoleukodystrophy in female heterozygotes: Underrecognized and undertreated

Parastoo Jangouk, Kathleen M. Zackowski, Sakkubai Naidu, Gerald V. Raymond

Research output: Contribution to journalReview article

29 Citations (Scopus)

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease resulting from mutations in the gene ABCD1 and alterations in peroxisomal beta-oxidation of long chain fatty acids. As it has been frequently discussed, it manifests a wide range of phenotypes in male, with progressive myelopathy being the most common. Even though the gene is localized to the X-chromosome and a region subject to X-inactivation, female carriers still are affected significantly by this condition. It has been stated that between 20 and 50% of women who are carriers may manifest some symptoms and recent evidence has suggested the differences in disease manifestations and relative rates of progression between men and women. However there have been only limited studies specifically addressing this and to date there has been no comprehensive review discussing the different phenotypes in female carriers, as well as the differences in disease onset, progression, disability, nervous system pathology and neuroimaging patterns compared to affected males. This is of key importance as similarities and differences between genders will assist in determining how best to target therapies in all affected individuals as opportunities for treatment present themselves. As will be further addressed in this review, we need to improve our understanding of the associations of emergent neuroimaging techniques to physical disability in this population. We reviewed the clinical presentations in the carrier population, the distinct disability profile and neuroimaging findings in order to put together pieces of this neglected segment in X-ALD and give direction to further studies.

Original languageEnglish (US)
Pages (from-to)180-185
Number of pages6
JournalMolecular Genetics and Metabolism
Volume105
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Adrenoleukodystrophy
Neuroimaging
Heterozygote
Genes
Neurodegenerative diseases
Phenotype
X Chromosome Inactivation
Spinal Cord Diseases
Neurology
X Chromosome
Pathology
Chromosomes
Neurodegenerative Diseases
Nervous System
Population
Disease Progression
Fatty Acids
Oxidation
Mutation
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Jangouk, Parastoo ; Zackowski, Kathleen M. ; Naidu, Sakkubai ; Raymond, Gerald V. / Adrenoleukodystrophy in female heterozygotes : Underrecognized and undertreated. In: Molecular Genetics and Metabolism. 2012 ; Vol. 105, No. 2. pp. 180-185.
@article{22a7898886a8497f905c45e88ae06924,
title = "Adrenoleukodystrophy in female heterozygotes: Underrecognized and undertreated",
abstract = "X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease resulting from mutations in the gene ABCD1 and alterations in peroxisomal beta-oxidation of long chain fatty acids. As it has been frequently discussed, it manifests a wide range of phenotypes in male, with progressive myelopathy being the most common. Even though the gene is localized to the X-chromosome and a region subject to X-inactivation, female carriers still are affected significantly by this condition. It has been stated that between 20 and 50{\%} of women who are carriers may manifest some symptoms and recent evidence has suggested the differences in disease manifestations and relative rates of progression between men and women. However there have been only limited studies specifically addressing this and to date there has been no comprehensive review discussing the different phenotypes in female carriers, as well as the differences in disease onset, progression, disability, nervous system pathology and neuroimaging patterns compared to affected males. This is of key importance as similarities and differences between genders will assist in determining how best to target therapies in all affected individuals as opportunities for treatment present themselves. As will be further addressed in this review, we need to improve our understanding of the associations of emergent neuroimaging techniques to physical disability in this population. We reviewed the clinical presentations in the carrier population, the distinct disability profile and neuroimaging findings in order to put together pieces of this neglected segment in X-ALD and give direction to further studies.",
author = "Parastoo Jangouk and Zackowski, {Kathleen M.} and Sakkubai Naidu and Raymond, {Gerald V.}",
year = "2012",
month = "2",
day = "1",
doi = "10.1016/j.ymgme.2011.11.001",
language = "English (US)",
volume = "105",
pages = "180--185",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "2",

}

Adrenoleukodystrophy in female heterozygotes : Underrecognized and undertreated. / Jangouk, Parastoo; Zackowski, Kathleen M.; Naidu, Sakkubai; Raymond, Gerald V.

In: Molecular Genetics and Metabolism, Vol. 105, No. 2, 01.02.2012, p. 180-185.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Adrenoleukodystrophy in female heterozygotes

T2 - Underrecognized and undertreated

AU - Jangouk, Parastoo

AU - Zackowski, Kathleen M.

AU - Naidu, Sakkubai

AU - Raymond, Gerald V.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease resulting from mutations in the gene ABCD1 and alterations in peroxisomal beta-oxidation of long chain fatty acids. As it has been frequently discussed, it manifests a wide range of phenotypes in male, with progressive myelopathy being the most common. Even though the gene is localized to the X-chromosome and a region subject to X-inactivation, female carriers still are affected significantly by this condition. It has been stated that between 20 and 50% of women who are carriers may manifest some symptoms and recent evidence has suggested the differences in disease manifestations and relative rates of progression between men and women. However there have been only limited studies specifically addressing this and to date there has been no comprehensive review discussing the different phenotypes in female carriers, as well as the differences in disease onset, progression, disability, nervous system pathology and neuroimaging patterns compared to affected males. This is of key importance as similarities and differences between genders will assist in determining how best to target therapies in all affected individuals as opportunities for treatment present themselves. As will be further addressed in this review, we need to improve our understanding of the associations of emergent neuroimaging techniques to physical disability in this population. We reviewed the clinical presentations in the carrier population, the distinct disability profile and neuroimaging findings in order to put together pieces of this neglected segment in X-ALD and give direction to further studies.

AB - X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease resulting from mutations in the gene ABCD1 and alterations in peroxisomal beta-oxidation of long chain fatty acids. As it has been frequently discussed, it manifests a wide range of phenotypes in male, with progressive myelopathy being the most common. Even though the gene is localized to the X-chromosome and a region subject to X-inactivation, female carriers still are affected significantly by this condition. It has been stated that between 20 and 50% of women who are carriers may manifest some symptoms and recent evidence has suggested the differences in disease manifestations and relative rates of progression between men and women. However there have been only limited studies specifically addressing this and to date there has been no comprehensive review discussing the different phenotypes in female carriers, as well as the differences in disease onset, progression, disability, nervous system pathology and neuroimaging patterns compared to affected males. This is of key importance as similarities and differences between genders will assist in determining how best to target therapies in all affected individuals as opportunities for treatment present themselves. As will be further addressed in this review, we need to improve our understanding of the associations of emergent neuroimaging techniques to physical disability in this population. We reviewed the clinical presentations in the carrier population, the distinct disability profile and neuroimaging findings in order to put together pieces of this neglected segment in X-ALD and give direction to further studies.

UR - http://www.scopus.com/inward/record.url?scp=84856108588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856108588&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2011.11.001

DO - 10.1016/j.ymgme.2011.11.001

M3 - Review article

C2 - 22112817

AN - SCOPUS:84856108588

VL - 105

SP - 180

EP - 185

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 2

ER -