ACOX1 gain-of-function variation in a 10-years-old patient responsive to immunomodulating therapy.

A heterozygous gain-of-function variant in the acyl-CoA oxidase 1 (ACOX1) gene, c.710A>G (p.Asn237Ser), is known to cause Mitchell syndrome, a very rare progressive disorder characterized by episodic demyelination, sensory polyneuropathy, and hearing loss. Only eight patients have been described so far. A single patient has been treated with intravenous immunoglobulin administration, indicating clinical improvement. In this study, we describe a 10-year-old girl carrying the identical mutation, who presented with progressive sensorineural deafness, visual abnormalities, skin ichthyosis, and gait ataxia from infantile age with progressive worsening and loss of walking ability by the age of 10 years. Antioxidant therapies and monthly intravenous immunoglobulin infusions showed excellent clinical results: after 1 year of treatment, the child is now able to walk, run, and jump. We emphasize the importance of early genetic diagnosis since an effective treatment is available for this rare condition.

Frequency of SCN2A-related disorder in the regional epilepsy centre of brescia between 2002 and 2021.

OBJECTIVE: SCN2A gene pathogenic variants are associated with a wide phenotypic spectrum, encompassing epilepsy, developmental delay, and autism spectrum disorder. Researches conducted in Denmark have revealed a disease frequency of approximately 1/78,608 (0.0012%) live births in this population. We estimated the frequency of SCN2A-related disorder in the birth cohort of Brescia and its province between 2002 and 2021. METHODS: Frequency was calculated by ratio between patients with SCN2A pathogenic variant and the total number of live births at the Regional Epilepsy Center of Brescia, between 2002 and 2021. The number of births in Brescia and province was obtained from the Italian National Institute of Statistics (ISTAT). RESULTS: A frequency of 11/23,2678 births (0.0047%) was found. In comparison with Danish data, we noticed a higher frequency of the pathogenic variant in our population, even considering the same time frame (0.0035% of subjects born between 2006 and 2014). CONCLUSION: The frequency of SCN2A pathogenic variant among live births in Brescia and its Province between 2006 and 2014 was about three times that of Danish population; this difference was about four times if we consider the period from 2002 to 2021. More studies are needed to further delineate the frequency of SCN2A pathogenic variant in Italian population.