Acyl-CoA Oxidase I Deficiency (ACOX1)

Acyl-CoA oxidase I deficiency is a pan-ethnic, autosomal recessive disease caused by pathogenic variants in the ACOX1 gene. The condition is characterized by abnormal accumulation of fatty acids in the body, which leads to neurodegeneration. Onset of symptoms occurs in infancy and includes weak muscle tone, seizures, and unusual facial features. Some infants may exhibit polydactyly and hepatomegaly. Although individuals with this condition may initially learn to walk and talk, regression of developmental milestones usually occurs within the first few years of life. Progression of the disease can lead to severe epilepsy, eventual loss of vision and hearing, and respiratory complications. Most affected individuals do not survive past childhood. No clear genotype-phenotype correlation has been observed.

Acute infantile liver failure is an autosomal recessive disease caused by pathogenic variants in the TRMU gene. Due to a founder mutation, it is more common in Sephardic Jewish individuals from Yemen, although the condition has been reported in other ethnicities. The disease presents in infancy as poor feeding, vomiting, jaundice, irritability, and reduced activity. Liver dysfunction can result in transient liver failure. If patients survive the episodes of acute liver failure, development can be normal. Although few patients have been reported, it has been suggested that individuals with two missense variants have a better clinical prognosis than patients with a frameshift or splice site variant.

For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.