Evaluation of two approaches to lysosomal acid lipase deficiency patient identification: An observational retrospective study

Cebolla, J.J. (Universidad de Zaragoza) ; Irún, P. ; Mozas, P. (Universidad de Zaragoza) ; Giraldo, P.

Resumen: Background and aims: Lysosomal acid lipase deficiency (LALD) leads to the accumulation of cholesteryl esters and/or triglycerides (TG) in lysosomes due to the lack of the enzyme codified by the LIPA gene. The most common symptoms are dyslipidaemia and hypertransaminasemia, together with manifestations common to other lysosomal storage disorders (LSDs), including visceromegalies and elevated plasma biomarkers. Alteration of the lipid-liver profile (LLP) has been widely applied as a criterion for LALD screening, but the usefulness of biomarkers has not yet been explored. Our purpose was to explore the utility of plasma chitotriosidase activity (ChT) and CCL18/PARC concentration in addition to LLP to identify LALD patients in an observational retrospective study of two different sample collections.
Methods: Biological samples refining: Collection 1 (primary hypercholesterolemia suspected) included unrelated individuals with hyperlipidaemia and without LDLR, APOB and PCSK9 gene mutations (Set 1), and Collection 2 (LSD suspected) included individuals without definitive LSD diagnosis (Set 2). We assessed plasma LLP (total cholesterol and its fractions, TG concentration and transaminases activities), as well as plasma ChT and CCL18/PARC. All subjects with anomalous LLP and/or biomarker levels were LIPA sequenced.
Results: Twenty-four subjects showed altered LLP and/or biomarkers. We identified two LALD patients (one homozygous and one compound heterozygous) and one carrier of a novel LIPA variant.
Conclusions: The measurement of plasma ChT and CCL18/PARC combined with LLP will be a useful approach to identifying LALD patients in retrospective LALD patient studies.

Idioma: Inglés

DOI: 10.1016/j.atherosclerosis.2019.03.013

Año: 2019

Publicado en: Atherosclerosis 285 (2019), 49-54
ISSN: 0021-9150

Factor impacto JCR: 3.919 (2019)

Categ. JCR: PERIPHERAL VASCULAR DISEASE rank: 16 / 65 = 0.246 (2019) - Q1 - T1
Categ. JCR: CARDIAC & CARDIOVASCULAR SYSTEMS rank: 42 / 138 = 0.304 (2019) - Q2 - T1

Factor impacto SCIMAGO: 1.515 - Cardiology and Cardiovascular Medicine (Q1)

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)