Inherited white matter disorders

Gene: ACBD5

Green List (high evidence)

At least 3 unrelated families reported to date with white matter disease due to biallelic variants in this gene. Supporting in vitro functional assays demonstrating ACBD5 deficiency leading to accumulation of very long-chain fatty acids due to impaired peroxisomal β-oxidation

- PMID: 23105016 (2013): Three siblings of a Saudi family with a truncating variant in ACBD5 (c.1205‐1G>A, p.Gly402Aspfs5*) and cone‐rod dystrophy, developmental delay, spastic paraparesis, and white matter disease

- PMID: 27799409 (2017): Single individual who presented with progressive leukodystrophy, cleft palate, ataxia and retinal dystrophy. Targeted sequencing revealed a homozygous variant in ACBD5 (c.626-689_937-234delins936+1075_c.936+1230inv, p.D208Vfs*30). Functional assay supports ACBD5 deficiency leads to accumulation of very long-chain fatty acids due to impaired peroxisomal β-oxidation

- PMID: 33427402 (2021): 36 year old female with retinal dystrophy, leukodystrophy, and psychomotor regression that started at 3 years old due to a novel homozygous variant in ACBD5 (c.1467G>A, p.Trp489*)

Created: 21 Apr 2021, 10:01 a.m. | Last Modified: 21 Apr 2021, 10:01 a.m.

Panel Version: 1.87

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Retinal dystrophy with leukodystrophy, OMIM:618863

Publications

• 23105016
• 27899449
• 27799409
• 33427402

Comment on list classification: This gene is awaiting curator evaluation and rating.

Created: 19 Dec 2018, 1 p.m.

Green List (high evidence)

Two unrelated families reported in the literature, plus functional evidence. Another variant in ClinVar. Consider Amber if not Green.

Created: 23 Jul 2018, 6:40 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 27799409, 27899449, 23105016

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