Adult onset leukodystrophy

Gene: ABCD1

The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 4:39 p.m. | Last Modified: 24 Feb 2025, 4:39 p.m.

Panel Version: 5.4

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Green List (high evidence)

Lucy Jackson (NHS) recommends that the mode of inheritance for ABCD1 should be changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (maybe less severe, later onset than males), to reflect that "heterozygous females are not at increased risk to develop CALD, but are at increased risk to develop AMN and primary adrenocortical insufficiency with increasing age" (https://www.ncbi.nlm.nih.gov/books/NBK1315/)

Created: 10 Oct 2024, 4:04 p.m. | Last Modified: 10 Oct 2024, 4:04 p.m.

Panel Version: 5.2

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Green List (high evidence)

Should be updated to also filter in heterozygous results for females. See https://www.ncbi.nlm.nih.gov/books/NBK1315/

Created: 27 Aug 2024, 1:10 p.m. | Last Modified: 27 Aug 2024, 1:10 p.m.

Panel Version: 5.1

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

I don't know

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Adrenoleukodystrophy, Adrenomyeloneuropathy, adult, 300100

I don't know

Review and rating uploaded from file (Consensus gene list for R62 Adult-Onset Leukodystrophy - Leeds.xlsx) submitted by Ian Berry (Leeds Genetics Laboratory) on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group. Phenotype and MOI not submitted.

Created: 4 Jul 2019, 4:32 p.m. | Last Modified: 4 Jul 2019, 4:32 p.m.

Panel Version: 0.10

Green List (high evidence)

Included all genes listed in clinical cases in Lynch et al 2015 PMID:28334938 and Ayrignac et al. 2015 PMID: 25527826. Included all genes with clear adult onset listed in Vanderver 2017 PMID:27159321 and Ahmed et al. 2017 PMID:24357685. A small number of genes from these resources were omitted, particularly those with limited or single case reports referenced in Ahmed et al, those with a metabolic basis (that could be determined by standard metabolic assays), and recessive diseases where the likelihood of encountering incidental carrier status is far more likely than finding a diagnosis e.g. Cockayne syndrome. Due to variable expressivity and potential later onset of phenotype in hypomorphic cases, peroxisomal biogenesis disorders OMIM phenotypic Series PS214100 and GeneReviews PMID:20301621 included.

Created: 4 Jul 2019, 4:06 p.m. | Last Modified: 4 Jul 2019, 4:06 p.m.

Panel Version: 0.9

Publications

• 28334938
• 25527826
• 27159321
• 24357685
• 20301621

Variants in this GENE are reported as part of current diagnostic practice