Peroxisomal acyl-CoA oxidase deficiency (ACOX1 deficiency)
General description
Peroxisomal acyl-CoA oxidase deficiency (ACOX1 deficiency) is a rare autosomal recessive neurodegenerative disorder characterized by impaired peroxisomal β-oxidation of very-long-chain fatty acids (VLCFAs). This deficiency results in systemic VLCFA accumulation, leading to progressive leukodystrophy, neuroinflammation, and severe neurological deterioration.
Clinical manifestations
The clinical presentation of ACOX1 deficiency is marked by a biphasic course: an initial period of developmental stagnation followed by rapid neurological regression. Neonates often exhibit hypotonia, weak suckling reflexes, and seizures. Dysmorphic facial features, including hypertelorism, a low nasal bridge, and low-set ears, are observed. Hepatomegaly and polydactyly may also occur.
Between ages 1–3 years, affected children experience developmental regression, losing previously acquired motor and language skills. Hypotonia evolves into hypertonia and hyperreflexia, accompanied by progressive spastic quadriparesis. Epilepsy worsens in frequency and severity, often becoming refractory to antiepileptic drugs. Sensorineural hearing loss, optic atrophy, and visual impairment emerge as the disease advances, with most patients succumbing to respiratory failure or sepsis by early childhood. Rare adult-onset cases exhibit milder phenotypes, characterized by cerebellar ataxia, brainstem atrophy, and late-onset seizures.
References
- Masson, Riccardo, et al. "Early white matter involvement in an infant carrying a novel mutation in ACOX1." European Journal of Paediatric Neurology 20.3 (2016): 431-434.
- Suzuki, Yasuyuki, et al. "Peroxisomal acyl CoA oxidase deficiency." The Journal of pediatrics 140.1 (2002): 128-130.
T2WI and FLAIR hyperintensity
Brain MRI in ACOX1 deficiency reveals a distinct pattern of leukodystrophy that progresses rostrocaudally. Initial involvement is observed in the medulla oblongata and cerebellar white matter, manifesting as T2-weighted hyperintensities in the middle cerebellar peduncles and dentate nuclei.
As the disease advances, signal abnormalities extend to the cerebral peduncles, corticospinal tracts, and periventricular white matter