Acyl-CoA oxidase deficiency

Children are born with this condition and their symptoms can be seen immediately.[2] In the early stages these can appear quite mild; weak muscle tone (often extreme hypotonia), lack of neonatal reflexes, seizures and abnormal (dysmorphic) facial features such as widely spaced eyes, a low nasal bridge, low set ears and an abnormally large forehead.[1][2] Due to the nature of the disease, in the build-up of VLCFAs, symptoms worsen progressively over time.[4] Children can often reach the stage at which they begin to walk and talk, before experiencing a rapid decline in motor skills due to demyelination and subsequent nerve damage.[2][3] A hearing deficit may develop, eyesight and response to visual and physical stimuli begins to diminish and eventually becomes non-existent.[1][2] The life expectancy of an individual with ACOX1 deficiency is 5 years.[2][3]

Acyl-CoA oxidase deficiency is an autosomal recessive disorder that is caused by biallelic pathogenic variants in ACOX1.[1][5] This is the gene that codes for the production of an enzyme called peroxisomal straight-chain acyl-CoA oxidase which is responsible for the breakdown of VLCFAs.[1][2] It is not completely clear how the build-up of these VLCFAs causes the symptoms seen with this condition, however research suggests that this abnormal accumulation triggers an inflammation in the nervous system which leads to demyelination.[1] Demyelination leads to the loss of white matter, leukodystrophy, in the brain and spinal cord.[1][5] It is this leukodystrophy that is related to the development of neurological abnormalities in people with Acyl-CoA oxidase deficiency.[5] Acyl-CoA oxidase deficiency is an extremely rare condition.[1]

Diagnosis can be done both prenatally based on family history and after birth based on clinical suspicion.[1][5] The primary prenatal diagnosis techniques involve the assessment of amniotic fluid for an abnormal elevation in VLCFAs, and a reduced presence (or in some cases complete absence) of acyl-CoA oxidase in fibroblasts. If the causative variants in a family are known, prenatal diagnosis can be performed by molecular testing.[4] After birth, there are a number of diagnostic techniques available for use. A blood sample can be taken, from which the serum levels of VLCFAs and acyl-CoA oxidase activity can be assessed. Analysis of VLCFAs is important for the identification of ACOX1 deficiency, if a leukodystrophy has been identified[5] Since the condition is genetic, and is caused by pathogenic variants in ACOX1, it can be confirmed by sequence or copy number analysis.[1] Due to the rarity of this condition, people who have it may not be diagnosed early in their disease progression. As a result, acyl-CoA oxidase deficiency may be misdiagnosed as similar conditions such as Usher syndrome and neonatal adrenoleukodystrophy.[5][6]

There are no cures for ACOX1 deficiency, supportive care is used to manage specific clinical symptoms for affected individuals.[1] Treatment is based upon symptoms, with the aim the provide some relief.[5] Pharmacologic agents are used to help improve muscle tone (management of dystonia) and to block neurological signalling to the muscle. Physical therapy is used to improve movement and function.[5] For the specific treatment of recurrent seizures, there are both pharmaceutical and surgical options.[5]