Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy

Kachwala, Isha; Regelmann, Molly O.

doi:10.3390/ijns8010018

Cited by 8 publications

(6 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Life-threatening adrenal crisis may occur and requires prompt treatment. 32 Mineralocorticoid function often remains intact, likely because VLCFAs accumulate to a lesser degree in the zona glomerulosa than the other regions within the adrenal cortex. 31 However, aldosterone deficiency has been observed in X-ALD and manifests with salt-craving.…”

Section: Dovepressmentioning

confidence: 99%

See 1 more Smart Citation

ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy

Volmrich¹,

Cuénant²,

Forghani³

et al. 2022

TACG

View full text Add to dashboard Cite

Pathogenic variants in the ABCD1 gene on the X chromosome may result in widely heterogenous phenotypes, including adrenomyeloneuropathy (AMN). Affected males typically present in their third or fourth decade of life with progressive lower limb weakness and spasticity, and may develop signs and symptoms of adrenal insufficiency and/or cerebral demyelination. Heterozygous females may be asymptomatic, but may develop a later-onset and more slowly progressive spastic paraparesis. In this review, we describe the clinical presentation of AMN, as well as its diagnosis and management. The role of rehabilitative therapies and options for management of spasticity are highlighted.

show abstract

Section: Dovepressmentioning

confidence: 99%

“…If untreated, it causes hyponatremia, hyperkalemia, mild metabolic acidosis, and may result in hypotension. 32 …”

Section: Introductionmentioning

confidence: 99%

ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy

Volmrich¹,

Cuénant²,

Forghani³

et al. 2022

TACG

View full text Add to dashboard Cite

show abstract

“…In addition to adrenal androgen deficiencies, primary testicular dysfunction is known to be a manifestation of disease among men with ALD. However, a recent review found sparse reports of the effects of low testosterone in ALD 90 . Potential contribution of low testosterone to cognition and mental health might be estimated from the broader literature on low testosterone, which can be associated with depression and lower scores on neurocognitive testing, including memory, processing speed, attention, visuospatial, and language skills 91–93 .…”

Section: Males With Aldmentioning

confidence: 99%

“…However, a recent review found sparse reports of the effects of low testosterone in ALD. 90 Potential contribution of low testosterone to cognition and mental health might be estimated from the broader literature on low testosterone, which can be associated with depression and lower scores on neurocognitive testing, including memory, processing speed, attention, visuospatial, and language skills. [91][92][93] However, the weight of this contribution to the neuropsychological presentation of adults with ALD is presently unclear and worth further investigation.…”

Section: Impact Of Endocrine Dysfunction On Neuropsychological Statusmentioning

confidence: 99%

Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening

Pierpont

Isaia

McCoy

et al. 2022

J of Inher Metab Disea

View full text Add to dashboard Cite

X-linked adrenoleukodystrophy (ALD) is a rare inherited neurological disorder that poses considerable challenges for clinical management throughout the lifespan. Although males are generally more severely affected than females, the time course and presentation of clinical symptoms are otherwise difficult to predict. Opportunities to improve outcomes for individuals with ALD are rapidly expanding due to the introduction of newborn screening programs for this condition and an evolving treatment landscape. The aim of this comprehensive review is to synthesize current knowledge regarding the neurocognitive and mental health effects of ALD. This review provides investigators and clinicians with context to improve case conceptualization, inform prognostic counseling, and optimize neuropsychological and mental health care for patients and their families. Results highlight key predictive factors and brainbehavior relationships associated with the diverse manifestations of ALD. The review also discusses considerations for endpoints within clinical trials and identifies gaps to address in future research.

show abstract

“…The correct interpretation of the pathogenicity of a variant ABCD1 is especially important. The identification of an inherited gene mutation can lead to a life-changing diagnosis of ALD in members of an extended family [ 9 , 10 ]. Genetic testing of X-linked ALD and screening of neonates have helped identify novel variants of unknown significance (VUSs), highlighting the need for further genetic characterization.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1

Zheng

Lin

et al. 2023

JCM

View full text Add to dashboard Cite

Cerebral adrenoleukodystrophy (CALD) is a fatal genetic disease characterized by rapid, devastating neurological decline, with a narrow curative treatment window in the early stage. Non-canonical splice-site (NCSS) variants can easily be missed during genomic DNA analyses, and only a few of them in ABCD1 have been explored. Here, we studied a Chinese patient with clinical features similar to those of early-stage CALD but with a negative molecular diagnosis and a sibling who had presumably died of CALD. Trio-based whole-exome sequencing (trio-WES) and RNA sequencing (RNA-Seq) revealed a novel hemizygote NCSS variant c.901-25_901-9 del in ABCD1 intron 1, resulting in a complex splicing pattern. The in vitro minigene assay revealed that the c.901-25_901-9 del construct contained two aberrant transcripts that caused skipping of exon 2 and a small 48-bp deletion on left of the same exon. We identified a novel NCSS variant, that extends the spectrum of the known ABCD1 variants, and demonstrated the pathogenicity of this gene variant. Our findings highlight the importance of combining RNA-Seq and WES techniques for prompt diagnosis of leukodystrophy with NCSS variants.

show abstract

Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy

Cited by 8 publications

References 50 publications

ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy

ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy

Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening

Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1

Contact Info

Product

Resources

About