ACOX1 Gain‐of‐Function and De Novo ROBO1 Variant in ACOX1 ‐ sEDD

ABSTRACT

ACOX1 ‐sEDD is an ultrarare neurocutaneous disorder caused by gain‐of‐function variants in ACOX1 , leading to excessive oxidative activity and multisystem injury. We report a male infant who, from the second week of life, developed a generalized erythematous desquamative greasy eruption with sparse dysplastic ocher‐colored scalp hair, followed by recurrent bilateral corneal epithelial defects, progressive hypotonia, failure to thrive, and seizures with diffuse symmetric leukoencephalopathy on brain MRI. Metabolic testing showed elevated dicarboxylic acids and medium‐/long‐chain acylcarnitines despite normal very‐long‐chain fatty acids and classical peroxisomal biomarkers, and trio exome sequencing identified de novo ACOX1 c.710A>G (p.Asn237Ser) and ROBO1 c.572delG (p.Cys191fs) variants. Cutaneous disease resolved with topical 10% N‐acetylcysteine and emollients, in conjunction with oral N‐acetylcysteine and adjunctive antioxidant vitamin therapy, while ocular involvement improved with vitamin A ointment and autologous serum eyedrops, supporting early recognition of ACOX1 ‐sEDD in infants with inflammatory ichthyosiform dermatitis and ocular‐neurologic involvement and suggesting that additional neurodevelopmental variants may modify disease expression.