Autosomal recessive hypercholesterolemia in Spain

[EN]Background and aims: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. W...

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Bibliographic Details
Authors: Sánchez-Hernández, Rosa María, Prieto Matos, Pablo, Civeira, Fernando, Lafuente, Eduardo Esteve, Vargas, Manuel Frías, Real, José T., Goicoechea, Fernando Goñi, Fuentes, Francisco J., Pocovi, Miguel, Boronat, Mauro, Wägner, Ana María, Masana, Luis
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Universidad de Salamanca (USAL)
Repository:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/155663
Online Access:http://hdl.handle.net/10366/155663
Access Level:Open access
Keyword:Familial hypercholesterolemia
Autosomal recessive hypercholesterolemia
LDLRAP1
Description
Summary:[EN]Background and aims: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain. Methods: Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed. Results: Seven patients with ARH were identified, 6 true homozygous and one compound heterozygous with a novel mutation: c.[863C>T];p.[Ser288Leu]. High genetic heterogeneity was found in this cohort. True homozygous subjects for LDLRAP1 have more severe phenotypes than the compound heterozygous patient, but similar to patients with homozygous familial hypercholesterolemia (HoFH). Cardiovascular disease was present in 14% of the ARH patients. LDL-C under treatment was above 185 mg/dl and the response to PCSK9 inhibitors was heterogeneous. Finally, the estimated prevalence in Spain is very low, with just 1 case per 6.5 million people. Conclusions: ARH is a very rare disease in Spain, showing high genetic heterogeneity, similarly high LDLC concentrations, but lower incidence of ASCVD than HoFH.