Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency

Abstract Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age. Here, we report two siblings with ACOX1 born non-consanguineous Japanese parents. They showed mild global delay infancy began regress at 5 years 10 months 6 months age respectively. gradually manifested cerebellar ataxia, dysarthria, pyramidal signs, dysphasia. Brain MRI revealed T2 high-intensity areas in the white matter, bilateral middle peduncle, transverse tracts pons, followed progressive atrophy these areas. Intriguingly, ratios C24:0, C25:0, C26:0 C22:0 plasma, which usually increase were within normal ranges both patients. On other hand, whole exome sequencing novel compound heterozygous variants ACOX1: frameshift variant (c.160delC:p.Leu54Serfs*18) missense (c.1259 T > C:p.Phe420Ser). The plasma concentration individual very long chain fatty acids (C24:0, C26:0) was elevated, found that peroxisomes fibroblasts patients larger size fewer number as previously reported deficiency. Furthermore, C24:0 ?-oxidation activity dramatically reduced. Our findings suggest elevation concentration, genetic analysis including analysis, biochemical studies on patient’s should be considered for correct diagnosis