Gene/phenotype/disorder under study
ACBD5 (OMIM *616618, OMIM Phenotype #618863)
Abstract
ACBD5 encodes a peroxisomal membrane protein with a dual function. It mediates the import of very long chain fatty acids (VLCFAs) into peroxisomes for β-oxidation and acts as a tethering protein at peroxisome–endoplasmic reticulum (ER) contact sites, facilitating lipid transfer between these organelles. Consequently, ACBD5 deficiency is expected to impair multiple aspects of peroxisomal function, including VLCFA degradation, ether lipid synthesis, and peroxisomal membrane maintenance.
Biallelic ACBD5 variants have hitherto been linked to disease phenotypes in only 14 individuals worldwide. The phenotypic spectrum includes early-onset retinal cone-rod dystrophy and progressive neurological manifestations such as spasticity, cerebellar ataxia, tremor, seizures, peripheral neuropathy, mildly elevated VLCFAs, and leukodystrophy on brain MRI. Monoallelic ACBD5 variants have also been associated with disease phenotypes, including isolated retinal dystrophy and thrombocytopenia, but their clinical relevance remains uncertain.
We have identified several previously unreported pedigrees with ACBD5 variants. Our aim is to perform a comprehensive phenotypic characterization and define the natural history of ACBD5-associated disease in a large international cohort.
Coordinating clinicians
Dr Francesca Magrinelli – f.magrinelli@ucl.ac.uk
Dr Grazia Falcon – 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
3- Linked to a translational/basic research project: No