Gene/phenotype/disorder under study
ACOX1 (OMIM *609751, OMIM Phenotypes # 618960, # 264470)
Abstract
The ACOX1 gene encodes the acyl-CoA oxidase 1, the first and rate-limiting enzyme of the peroxisomal β-oxidation pathway which catalyses the desaturation of very-long-chain fatty acyl-CoAs. ACOX1 deficiency leads to impaired peroxisomal fatty acid oxidation and accumulation of very-long-chain fatty acids, with disruption of cell lipid homeostasis.
Biallelic variants in ACOX1 have been linked to disease phenotypes in few individuals worldwide. The phenotypic spectrum includes early-onset neurodegeneration, hypotonia, developmental delay, seizures, and leukodystrophy on brain MRI. In addition, monoallelic variants in ACOX1 cause Mitchell syndrome, a distinct condition characterized by episodic inflammatory attacks, progressive sensorimotor neuropathy, hearing loss, and central nervous system involvement. Overall, the number of reported cases remains limited, and the full phenotypic spectrum and natural history are not well defined. We have identified additional unpublished individuals with ACOX1 variants. Our aim is to establish an international cohort to better delineate the clinical spectrum, refine genotype–phenotype correlations, and improve understanding of disease progression.
Coordinating clinicians
Dr Francesca Magrinelli – f.magrinelli@ucl.ac.uk
Dr Grazia Falcone – g.falcone@ucl.ac.uk
Institution
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: : Yes (Not mandatory)
2- Resampling of patients: Yes (Not mandatory)
3- Linked to a translational/basic research project: No