Instituto de Investigación Sanitaria Aragón (IIS Aragón), GIIS-012, Zaragoza, 50009, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), CB/06/07/1036, Instituto de Salud Carlos III (ISCIII), Hospital Universitario Miguel Servet, Zaragoza, 50009, Spain; Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y Otras Lisosomales (FEETEG), Zaragoza, 50008, Spain; Departamento de Bioquímica, Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, 50009, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), CB/06/07/1036, Instituto de Salud Carlos III (ISCIII), Hospital Universitario Miguel Servet, Zaragoza, 50009, Spain.
Atherosclerosis. 2019 Jun;285:49-54. doi: 10.1016/j.atherosclerosis.2019.03.013. Epub 2019 Mar 18.
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.
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.
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.
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.
由于缺乏由 LIPA 基因编码的酶，溶酶体酸性脂肪酶缺乏症 (LALD) 导致胆固醇酯和/或甘油三酯 (TG) 在溶酶体中积累。最常见的症状是血脂异常和高转氨酸血症，以及其他溶酶体贮积症 (LSD) 的常见表现，包括内脏肿大和血浆生物标志物升高。脂质-肝脏谱 (LLP) 的改变已广泛应用于 LALD 筛查标准，但生物标志物的有用性尚未得到探索。我们的目的是在对两个不同样本集的观察性回顾性研究中，除了 LLP 外，还探讨血浆壳聚糖酶活性 (ChT) 和 CCL18/PARC 浓度在识别 LALD 患者中的作用。
生物样本的精炼：收集 1 （原发性高胆固醇血症疑似）包括与高脂蛋白血症无关且无 LDLR、APOB 和 PCSK9 基因突变的个体（集 1），收集 2 （LSD 疑似）包括无明确 LSD 诊断的个体（集 2）。我们评估了血浆 LLP（总胆固醇及其分数、TG 浓度和转氨酸活性），以及血浆 ChT 和 CCL18/PARC。所有 LLP 和/或生物标志物水平异常的受试者均进行了 LIPA 测序。
24 名受试者显示 LLP 和/或生物标志物改变。我们鉴定了两名 LALD 患者（一名纯合子和一名复合杂合子）和一名新型 LIPA 变异携带者。
联合 LLP 测量血浆 ChT 和 CCL18/PARC 将是识别回顾性 LALD 患者研究中 LALD 患者的有用方法。
