Retinal Dystrophy and Leukodystrophy Caused by ACBD5 Deficiency in Five Omani Patients: A Case Series

Acyl-coenzyme A-binding domain-containing protein 5 (ACBD5) is an acyl-CoA-binding peroxisomal membrane protein. Its deficiency impairs peroxisomal beta-oxidation of very long-chain fatty acids and causes an autosomal recessive disorder that manifests as retinal dystrophy and leukodystrophy. We report five Omani patients with ages ranging between 4 and 30 years. First presentation was in infancy with nystagmus and photophobia and progressed to legal blindness by 10 years of age. Electroretinogram confirmed severe cone-rod dystrophy. Motor neuroregression with variable ages of onset and signs of progressive cerebellar ataxia were seen in all patients, whereas cognitive decline was observed in some. Brain MRI revealed diffuse T2 signal abnormality in deep white matter, with involvement of corticospinal tracts. Plasma long chain fatty acid profile showed mild elevation of C26 and C26/22 ratio. Two homozygous variants in ACBD5 gene were identified; exons 7 and 8 deletion and exon 4 deletion. This series confirms retinal dystrophy and leukodystrophy as key features of ACBD5 deficiency with main symptoms of early onset visual decline, progressive spasticity, and cerebellar ataxia. This case series adds valuable insight in to this ultra-rare neurometabolic disease.