Rapid lipid-lowering response in two cases of autosomal recessive hypercholesterolemia
Makaleler > Tam Makale · 2025
Yazarlar: Havva YAZICI, Fehime Erdem, Ebru Canda, Sema Kalkan Uçar, Sema KALKAN UÇAR, Mahmut ÇOKER
JOURNAL OF CLINICAL LIPIDOLOGY, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Scopus, 2025, cilt 19, ss 167-172
DOI: 10.1016/j.jacl.2024.09.003
Özet
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.