Rapid lipid-lowering response in two cases of autosomal recessive hypercholesterolemia.

BACKGROUND

Autosomal recessive hypercholesterolemia (ARH) is an ultrarare dyslipidemia caused by variants in the LDLRAP1 gene. Clinically, this condition is indistinguishable from other homozygous familial hypercholesterolemia (HoFH).

CASE: We present the cases of 2 siblings diagnosed with ARH caused by LDLRAP1 gene c.617-14C > A splicing homozygous variant. Over a 5-year treatment period, the older sibling experienced an 81% reduction in low-density lipoprotein cholesterol (LDL-C) levels with the maximal dose of pitavastatin plus ezetimibe, while the younger sibling achieved a 75% reduction. After three sessions, the older brother no longer required LDL apheresis, and the sibling never had LDL apheresis.

CONCLUSION

Our findings demonstrate a rapid and significant response to lipid-lowering therapy (LLT) in patients with ARH caused by c.617-14C > A splicing VUS variant, a condition that mimics HoFH at diagnosis. Long-term follow-up studies in large pediatric cohorts of ARH patients treated with pitavastatin plus ezetimibe from childhood are necessary to better define the risk of cardiovascular disease (CVD) development.