Reduced LDL receptor expression and LDL uptake in lymphoblastoid cells from a patient with cholesteryl ester storage disease

Lysosomal acid lipase deficiency (LAL-D) is characterized by severe dyslipidemia, including elevated LDL cholesterol, despite activation of sterol-responsive pathways. We investigated whether altered receptor-mediated LDL catabolism may contribute to this phenotype. EBV-transformed lymphoblastoid cells from a patient with cholesteryl ester storage disease (CESD) homozygous for the LIPA Exon 8 Splice-Junction Mutation were compared with cells from heterozygous carriers, heterozygous familial hypercholesterolemia patients, and controls. LAL activity was measured using a fluorometric assay. LDL receptor (LDLR) surface expression and LDL internalization were assessed by flow cytometry. CESD cells displayed markedly reduced LAL activity together with modest but significant reductions in LDL receptor (LDLR) surface expression and LDL internalization. Under low-serum conditions, LDLR gene expression was also significantly lower in CESD cells than in controls. These findings suggest that impaired LDLR-mediated LDL uptake may contribute to dyslipidemia in LAL-D, alongside previously reported alterations in lipoprotein production. Confirmation in additional patients and disease-relevant cellular models is required.