Case Report of Dual Variants in SLC1A4 and APOE

ABSTRACT

Spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) is a rare autosomal recessive neurodevelopmental disorder linked to biallelic variants in the SLC1A4 gene, which encodes the ASCT1 amino acid transporter critical for neutral amino acid uptake in neurons. While SLC1A4 mutations are well established in SPATCCM, the potential impact of additional genetic factors on disease progression remains unexplored. We report a rare case of an 8‐month‐old male with severe global developmental delay and progressive microcephaly, identified with whole‐exome sequencing to have a novel combination of homozygous SLC1A4 (p.Arg457Trp) and heterozygous APOE (p.Cys130Arg) mutations. Neuroimaging revealed severe hypomyelination and diffuse white matter abnormalities. This is the first reported case of SPATCCM with an APOE variant, implicating a potential interplay between amino acid transport deficiencies and lipid metabolism in brain development.