X-linked adrenoleukodystrophy caused by maternal ABCD1 mutation and paternal X chromosome inactivation

Exp Ther Med. 2022 Jul 12;24(3):565. doi: 10.3892/etm.2022.11502. eCollection 2022 Sep.


X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It is caused by defects in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, resulting in impaired peroxisomal β-oxidation of very-long-chain fatty acids (VLCFAs). As an X-linked recessive disease, female X-ALD carriers are typically asymptomatic. In the present study, a 7-year-old girl was diagnosed with cerebral ALD. Brain magnetic resonance imaging revealed asymmetric demyelination of bilateral white matter. Plasma VLCFAs level showed a substantial increase. Whole exome and Sanger sequencing revealed an ABCD1 c.919C>T (p.Q307X) heterozygous pathogenic mutation, which was inherited from the asymptomatic mother. X chromosome inactivation (XCI) analysis revealed that the normal paternal X chromosome was almost completely inactivated. Thus, the maternal ABCD1 mutation and paternal XCI were responsible for causing the disease in the patient. XCI may be one reason female X-ALD carriers can be symptomatic.

Keywords: ATP-binding cassette subfamily D member 1; X chromosome inactivation; X-linked adrenoleukodystrophy; very-long-chain fatty acid; whole exome sequencing.

Grants and funding

Funding: The present study was supported by the 345 Talent Project of Shengjing Hospital (grant no. M0298).