Child Neurology: Neurodegenerative Encephalomyelopathy Associated With ACOX1 Gain-of-Function Variation Partially Responsive to Immunotherapy.
Neurology
; 99(8): 341-346, 2022 08 23.
Article
in En
| MEDLINE
| ID: mdl-35715200
ABSTRACT
Acyl-CoA oxidase 1 (ACOX1) is a peroxisomal enzyme involved in beta-oxidation of very-long-chain fatty acids. Although loss of function of ACOX1 had been previously described, gain-of-function variation of ACOX1 gene has been only recently identified, with a paucity of known cases. Gain-of-function variation results in overproduction of reactive oxygen species, resulting in progressive neurodegeneration with discrete relapses. We report the case of a 19-year-old woman with a 5-year history of longitudinally extensive posterior predominant myelopathy, bilateral corneal scars, and white matter lesions who presented with first-time seizure, progressive sensorineural hearing loss, ichthyosiform rash, and cauda equina syndrome. Extensive workup was unrevealing. The patient showed no response to high-dose steroids but stabilization and improvement with return to baseline over 6 months with IVIg and low-dose mycophenolate mofetil. Whole-exome sequencing performed 4 years before was nondiagnostic, but subsequent reanalysis revealed a heterozygous variation in the ACOX1 gene (NM_004035.6 c.710A>G, p.Asn237Ser), now considered to be pathogenic. This case reports a rare condition and highlights the importance of reanalysis of previously nondiagnostic genome/exome sequencing data. Furthermore, the patient's clinical stability for over 1 year on immunotherapy raises the possibility of disease modification in an otherwise universally fatal condition.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neurodegenerative Diseases
/
Acyl-CoA Oxidase
/
Immunotherapy
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
Language:
En
Journal:
Neurology
Year:
2022
Document type:
Article