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Autosomal recessive hypercholesterolemia in Spain

  • Rosa María Sánchez-Hernández
    Correspondence
    Corresponding author. Present/permanent address. Hospital Universitario Insular de Gran Canaria, Avenida Marítima Sin Número, CP: 35016, Las Palmas de Gran Canaria, Las Palmas, Spain.
    Affiliations
    Sección de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno Infantil de Gran Canaria, Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) de la Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
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  • Pablo Prieto-Matos
    Affiliations
    Unidad de Endocrinología Pediátrica, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Spain
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  • Fernando Civeira
    Affiliations
    Unidad Clínica y de Investigación en Lípidos y Arterioesclerosis, Hospital Universitario Miguel Servet, IIS Aragón, Centro de Investigación Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Universidad de Zaragoza, Zaragoza, Spain
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  • Eduardo Esteve Lafuente
    Affiliations
    Servicio Endocrinología y Nutrición, Hospital Universitari de Girona Dr. Josep Trueta, Spain
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  • Manuel Frías Vargas
    Affiliations
    Centro de Salud San Andrés, Madrid, Spain
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  • José T. Real
    Affiliations
    Servicio de Endocrinología y Nutrición, Hospital Clínico Valencia, Departamento de Medicina, Universidad de Valencia, INCLIVA, Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Spain
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  • Fernando Goñi Goicoechea
    Affiliations
    Servicio Endocrinología y Nutrición, Hospital Universitario de Basurto, Bilbao, Spain
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  • Francisco J. Fuentes
    Affiliations
    Hospital Universitario Reina Sofía, Universidad de Córdoba, Centro de Investigación Biomédica en Red de Fisiopatolgía de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Instituto Maimónedes de Investigación Biomédica de Córdoba (IMIBIC), Spain
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  • Miguel Pocovi
    Affiliations
    Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, IIS Aragón, CIBERCV, Zaragoza, Spain
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  • Mauro Boronat
    Affiliations
    Sección de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno Infantil de Gran Canaria, Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) de la Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
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  • Ana María Wägner
    Affiliations
    Sección de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno Infantil de Gran Canaria, Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) de la Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
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  • Luis Masana
    Affiliations
    Unidad de Medicina Vascular y Metabolica, Unidad de Investigación en Lipidos y Arterioesclerosis, Hospital Universitario "Sant Joan", Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Madrid, Spain
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      Highlights

      • Nation-wide prevalence of recessive hypercholesterolemia in Spain is 1:650,000.
      • Genetic mutations causing the disease are very heterogeneous.
      • Phenotype and response to therapy are better than in homozygous dominant forms.

      Abstract

      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 LDL-C concentrations, but lower incidence of ASCVD than HoFH.

      Keywords

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