ACOX1 is the gene that provides instructions for making peroxisomal straight-chain acyl-CoA oxidase, an enzyme involved in breaking down very-long-chain fatty acids inside peroxisomes.
Peroxisomes are small cell structures that help process fatty acids and other molecules. ACOX1 acts early in peroxisomal fatty-acid beta-oxidation and produces hydrogen peroxide as a by-product, which is normally handled by other peroxisomal enzymes such as catalase.
Function
The ACOX1 enzyme helps shorten very-long-chain fatty acids so they can be further processed. This pathway is important because some fatty acids are too long to be handled efficiently by mitochondria alone.
The gene is located on chromosome 17 and is also known by names such as acyl-CoA oxidase 1, palmitoyl-CoA oxidase and peroxisomal acyl-coenzyme A oxidase 1.
Disease Associations
Different kinds of ACOX1 variant can cause different clinical pictures.
Biallelic loss-of-function variants can cause peroxisomal acyl-CoA oxidase deficiency, a rare inherited disorder beginning in infancy. MedlinePlus Genetics describes hypotonia, seizures, developmental problems, leukodystrophy, hearing and vision loss, and early severe neurological decline in many reported cases.
Specific de novo gain-of-function variants have been reported in Mitchell syndrome, a rare autosomal dominant neurodegenerative disorder associated with episodic demyelination, peripheral neuropathy and hearing loss. The mechanism is different from classical loss-of-function acyl-CoA oxidase deficiency.
ACOX1 should not be confused with genes that cause other peroxisomal disorders. For example, X-linked adrenoleukodystrophy is mainly associated with ABCD1, and classic Refsum disease is commonly associated with PHYH or PEX7.
Diagnosis and Research
Diagnosis of suspected ACOX1-related disease may involve clinical assessment, biochemical testing of very-long-chain fatty acids, brain imaging, nerve studies and genetic testing.
Research has focused on how loss of enzyme function, gain of enzyme activity and oxidative stress affect glial cells, myelin and the nervous system. Because the conditions are rare, much of the literature is based on case reports, small series and experimental models.
See Also
References
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