Abstract Details

Title Neurodegenerative Encephalomyelopathy Associated with ACOX-1 Gain-of-Function Mutation Partially Responsive to Immunotherapy

Topic Child Neurology and Developmental Neurology

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 6-002

Objective To report a case of neurodegenerative encephalomyelopathy associated with the recently described Acyl-CoA Oxidase 1 (ACOX1) gain-of-function mutation who was responsive to immunotherapy.

Background ACOX1 is a peroxisoml enzyme involved in beta-oxidation of very long chain fatty acids. Although loss of function of ACOX-1 had been previously described, gain-of-function mutation of ACOX-1 gene has only been recently identified, with a paucity of known cases (1). Gain of function mutation results in over production of reactive oxygen species, resulting in progressive neurodegeneration with discrete relapses. To date, no known patient has lived in the third decade.

Design/Methods Case report from a pediatric tertiary referral center.

Results A 19-old-female with a 5-year history of longitudinally extensive posterior predominant myelitis, bilateral corneal scars, and white matter lesions of unknown etiology presented with first time seizure, progressive sensorineural hearing loss, icthiosyform skin rash, and acute cauda equina syndrome. Extensive neuroinflammatory, metabolic, and infectious work-up was unrevealing. The patient had no response to high dose steroids but clinical stabilization and subsequent improvement with return to baseline over six months with IVIg and low dose mycophenolate mofetil (300 mg/m2). Whole exome sequencing performed 4 years prior was non-diagnostic but subsequent reanalysis revealed a heterozygous mutation in the ACOX1 gene (NM_004035.6: c.710A>G, p.Asn237Ser), now considered to be pathologic.

Conclusions

This report raises clinical awareness of a recently described condition and highlights the importance of reanalysis of previously non-diagnostic genome/exome sequencing data when common conditions are reasonably ruled out. Further, the patient’s clinical stability for over one year on immunotherapy raises the possibility of utilization in an otherwise universally fatal condition.

Reference:
1- Chung HL, Wangler MF, Marcogliese PC, et al. Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron. 2020;106(4):589-60

Authors/Disclosures
Mellad Khoshnood, MD (Children's Hospital Los Angeles) PRESENTER	Dr. Khoshnood has nothing to disclose.
Saba Jafarpour, MD (Children’s Hospital of Los Angeles)	Dr. Jafarpour has nothing to disclose.
Jonathan Santoro, MD (Department of Neurology, Children's Hospital Los Angeles)	Dr. Santoro has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Santoro has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cycle Pharma. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Santoro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Down Syndrome Society.

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