Clinical and genetic characterization of homozygous <i>LDLR</i> variants in familial hypercholesterolaemia: insights from two case reports

Background: Familial hypercholesterolaemia (FH) is an inherited lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased risk of atherosclerotic cardiovascular disease. Despite its high prevalence, FH remains underdiagnosed and undertreated in many regions, particularly in low- and middle-income countries. Case summary: : c.1060+2T>G (rs774069731) in Case 1 and c.530C>T (rs121908026) in Case 2. The patients were managed with high-intensity statins, ezetimibe, PCSK9 inhibitors, inclisiran, and lipoprotein apheresis, which resulted in partial LDL-C reduction. Discussion: These cases highlight the genotypic and phenotypic heterogeneity of FH, with the c.1060+2T>G variant being reported for the first time in this region, thus expanding the known genetic spectrum of FH. Conclusion: This case series reinforces the importance of comprehensive clinical and genetic evaluation in patients with severe hypercholesterolaemia. Early diagnosis, intensified lipid-lowering strategies, and equitable access to advanced therapies are essential to improve outcomes in resource-constrained settings.