Elevated cholesterol is a common phenotype for dominant and recessive ATAD3-associated disorders

Recently, Muñoz-Oreja et al. 1 reported that elevated cholesterol functions as a compensatory mechanism to increase tolerance to pathological heterozygous dominant-acting ATAD3A variants, eventually leading to membrane-embedded cholesterol aggregation in the form of membrane whorls.This excess cholesterol is a cellular and pathological abnormality in ATAD3-associated disorder that can cascade to lysosomal insufficiency.Here we present a similar accumulation of free cholesterol and membrane whorls in two unrelated patients' cells carrying pathological biallelic ATAD3A variants.Our results suggest that increased cholesterol is a common cellular response in both, autosomal dominant and recessive ATAD3-associated disorders, supporting the premise reported by Muñoz-Oreja et al. 1