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Review
. 2020 Apr;31(2):56-61.
doi: 10.1097/MOL.0000000000000664.

Autosomal recessive hypercholesterolemia: update for 2020

Laura D'Erasmo  1 , Alessia Di Costanzo, Marcello Arca
Affiliations
Review

Autosomal recessive hypercholesterolemia: update for 2020

Laura D'Erasmo et al. Curr Opin Lipidol. 2020 Apr.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

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