Lysosomal acid lipase activity in children with dyslipidemia and hepatic dysfunction

Beyhan Özkaya; Ebru CANDA; Melis Köse; Mehtap Kağınıcı; Eser YILDIRIM SÖZMEN; Mahmut ÇOKER; Sema KALKAN UÇAR

doi:10.15761/ghe.1000205

Lysosomal acid lipase activity in children with dyslipidemia and hepatic dysfunction

Makaleler > Tam Makale · 2020

Yazarlar: Beyhan Özkaya, Ebru CANDA, Melis Köse, Mehtap Kağınıcı, Eser YILDIRIM SÖZMEN, Mahmut ÇOKER, Sema KALKAN UÇAR

Gastroenterology, Hepatology and Endoscopy, Hakemsiz Dergi, Uluslararası, 2020, cilt 5, ss 1-5

DOI: 10.15761/ghe.1000205

Özet

AbstractBackground: Lysosomal acid lipase (LAL) enzyme, is responsible for the hydrolysis of intracellular triacylglycerol and cholesterol esters. We investigate the LAL activity (LAL-A) in patients with hepatic dysfunction and/or dyslipidemia and determine the associated clinical and biochemical parameters.Methods: This prospective, cross-sectional study included 360 children (3 months -18 years; 40 control, and 320 screening patients). Demographic data, major clinical and laboratory findings, LAL-A and possible biomarkers were evaluated. Screening group was divided into two: LAL-A<0.6 nmol/ml/h (Group1); LAL-A ? 0.6 nmol/ml/h (Group 2). LAL-A predictive model was evaluated using logistic regression.Results: The mean LAL-A in the screening group (1.43 ± 2.05 (0.03-16.8) nmol/ml/h) was significantly reduced compare to controls (p < 0.001). No LAL deficiency was detected. There was a negative correlation between LAL-A and low-density lipoprotein cholesterol, triglyceride, and alanine aminotransferase (ALT) levels. LAL-A in patients with chronic fatigue (p = 0.002), hepatomegaly (p = 0.013) and splenomegaly (p = 0.001) were significantly lower compare to those without. The median thiobarbituric acid reactive substances, myeloperoxidase, chitotriosidase, hs-CRP, Citokeratinlevels in Group 1 were higher compare to the controls (p < 0.005). Conclusions:LAL-A was reduced in paediatric patients with dyslipidemia and/or elevated transaminase. Our final multivariable predictive model for reduced LAL-A included: ALT, triglyceride, and hepatomegaly. *Correspondence to:Sema Kalkan Uçar, Department of Pediatrics, Division of Metabolism and Nutrition, Ege University Medical Faculty, Bornova, Izmir, Turkey, Tel: 90.232.390.1037, E-mail: semakalkan@hotmail.comKey words: lysosomal acid lipase activity, pediatric patients Received: May 19, 2020; Accepted: June 15, 2020; Published: June 18, 2020Abbreviations: ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; BMI: Body Mass Index; CESD: Cholesteryl Ester Stor-age Disease; CI: Confidence Interval; HDL-C: Low-Density Lipoprotein Cholesterol; hsCRP: High-Sensitivity C-Reactive Protein; LAL: Lysosomal Acid Lipase; LAL-A: LAL activity; LDL-C: High-Density Lipoprotein Cho-lesterol; MPO: Myeloperoxidase; OR: Odds Ratio; R: Reduced; SR: Signifi-cantly Reduced; TBARS: Thiobarbituric Acid Reactive Substances.IntroductionPediatric lysosomal acid lipase (LAL) deficiency caused by LIPA gene mutations is associated with two phenotypes Wolman’s disease and Cholesteryl ester storage disease (CESD). Deficiency in LAL activity (LAL-A) (< 1% in Wolman’s disease, 1-12% of the normal in CESD) leads to impaired hydrolysis of intracellular triacylglycerol and cholesterol esters [1-3].Clinically, LAL deficiency is manifested by hepatosplenomegaly, hepatosteatosis, hepatic insufficiency, elevations in transaminases, total cholesterol, low-density lipoprotein cholesterol (LDL) and triglyceride levels, decreased in high-density lipoprotein cholesterol (HDL-C) and atherosclerosis [4]. So, lipid metabolism - dyslipidemia [1,5,6] and hepatic involvement [7] are hot topics in the in investigation of children with LAL deficiency. In this study, the aim was to perform a selective LAL-A screening in pediatric patients with hepatic dysfunction and/or dyslipidemia, and investigate the clinical and laboratory biomarkers chitotriosidase (used in the diagnosis and follow-up of lysosomal diseases), cytokeratin-18 (plays a role in apoptosis in non-alcoholic steatohepatitis), hsCRP (a valuable indicator in atherosclerosis and non-alcoholic steatohepatitis), thiobarb

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