D'Erasmo Laura, Di Costanzo Alessia, Arca Marcello
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Curr Opin Lipidol. 2020 Apr;31(2):56-61. doi: 10.1097/MOL.0000000000000664.
This review summarizes the current knowledge regarding autosomal recessive hypercholesterolemia (ARH) and provides new insight into the natural history and therapeutic management of this lipid disorder.
Novel homozygous and compound heterozygous ARH-causing mutations have been reported in the literature, to date. The long-term follow-up of a cohort of ARH patients demonstrated that, despite intensive treatment with conventional lipid-lowering therapies, their low-density lipoprotein (LDL) cholesterol levels remain far from target and this translates into a poor cardiovascular prognosis. ARH is also associated with increased risk of developing aortic valve stenosis. However, lomitapide, a microsomal triglyceride transfers protein inhibitor, may represent a new opportunity for the effective treatment of ARH.
ARH is an ultrarare disorder of LDL metabolism caused by mutations in the LDLRAP1 gene. It is inherited as a recessive trait and causative mutations, though heterogeneous, are all predicted to be loss-of-function. Recent investigations have demonstrated that ARH can be considered a phenocopy of homozygous familial hypercholesterolemia, where the risk of atherosclerotic cardiovascular diseases and aortic valve stenosis remains elevated despite conventional therapies. The combination of lomitapide with the conventional LDL-C-lowering medications appears to be a promising approach to treat this condition.
本综述总结了目前关于常染色体隐性高胆固醇血症（ARH）的知识，并为这种脂质紊乱疾病的自然史和治疗管理提供了新的见解。
迄今为止，文献中已报道了新的导致ARH的纯合子和复合杂合子突变。一组ARH患者的长期随访表明，尽管采用传统降脂疗法进行强化治疗，他们的低密度脂蛋白（LDL）胆固醇水平仍远未达到目标，这导致心血管预后不良。ARH还与主动脉瓣狭窄风险增加有关。然而，微粒体甘油三酯转运蛋白抑制剂洛美他派可能为ARH的有效治疗带来新机会。
ARH是一种由LDLRAP1基因突变引起的极其罕见的LDL代谢紊乱疾病。它作为隐性性状遗传，致病突变虽然具有异质性，但都预计会导致功能丧失。最近的研究表明，ARH可被视为纯合子家族性高胆固醇血症的拟表型，尽管采用传统疗法，动脉粥样硬化性心血管疾病和主动脉瓣狭窄的风险仍然很高。洛美他派与传统降低LDL-C的药物联合使用似乎是治疗这种疾病的一种有前景的方法。
