Studying the potential pre-indicators of cholesterol ester storage disease and determining the reference range of lysosomal acid lipase

Introduction and Aim: Cholesterol ester storage disease is a rare, lysosomal storage disease with autosomal recessive inheritance. It results from the deficiency or insufficiency of lysosomal acid lipase (LAL) enzyme in charge of the hydrolysis of intracellular triacylglycerol and cholesterol esters. The initial objective of the present study is to search for LAL deficiency in the cases with clinical suspicion (hepatic dysfunction and /or existence of dislipidemia). In the cases determined to have low LAL activity, the secondary objectives of our study are to determine the biomarkers with which this lowness will be associated and to determine the reference range of Turkish population for LAL. At the lead of the searched biomarkers, it was planned to search the relationship with "kitotriozidaz" used in the diagnosis and follow up of lysosomal diseases, with "cytokeratin-18" responsible for apoptosis in non-alcoholic steatohepatitis, with hsCRP which is a valuable marker in atherosclerosis and non-alcoholic steatohepatitis, and with TBARS and MPO which have important roles in lipid peroxidation. Material-Methods: A total of 360 children were included in the study with the age range of 0-18. 40 of them were included in the control group and other 320 were the non-obese scanning cases diagnosed with hepatomegaly (+/-), transaminase elevation (+/-) and/ or hyperlipidemia. Of these patients, those with LAL activity of <0.6 nmol/ml/hour formed Group 1; those with LAL activity of ≥0.6 nmol/ml/hour formed Group 2. The cases demographic data such as age, gender, family history of hyperlipidemia and results of physical examination were recorded. From the patient files, the results of lipid profile, hemogram, biochemistry, coagulation parameters, abdomen USG and viral serology (HbsAg, Anti Hbs, Anti HCV) were recorded. To study LAL activity, capillary dry blood sample was sorted out; in cases with low LAL activity blood was simultaneously sorted out into 2 cc plain tube to study kitotriosidasis , hsCRP, cytokeratin-18, MPO and TBARS. Sfingomyelinaz was studied as reference enzyme. LAL enzyme level was studied with enzyme inhibition (Lalistat 2 ) method. Results: Average age of all cases in the study was found to be 5 years (0-18). 154 of the cases (42%) were male and 206 of them (58%) were female. In the scan group, kin marriage and familial hyperlipidemia were found to be significantly high (p<0.05). Height and weight SDS averages were found to be significantly low in the scan group (p<0.05). LAL level in the scan group were found to be significantly low in comparison to control group (p<0.001), yet no case with LAL deficiency (LAL < 0.03 nmol/ml/hour) was found. When the control and scan groups were compared, hemoglobin and thrombocyte parameters were found to be significantly low in scan group (p<0.05). As might be expected, AST, ALT total bilirubin levels were found to be significantly high in scan group (p<0.05). When Group 1 was compared to control group, family history of hyperlipidemia, ALT, AST and total bilirubin were found to be significantly high ; Hemoglobin, leukocyte and platelets numbers were found to be significantly low in Group 1 (p<0.05). Also in Group 1, LDL-cholesterol and trigliserid were found to be significantly high, HDL-cholesterol to be significantly low (p<0.05). TBARS levels of Control group and Group 1were found to be significantly different (11.25 (3.75-49.38),14.38(5-37.5) mmol/ml, respectively) (p=0.035). No relationship was found with other parameters. Besides, in patients with hepatomegali, LAL activities were found to be significantly low (p=0.013). when the whole study group was assessed, a negative correlation was determined between LAL level and LDL, and between trigliserid and ALT. Also, it was seen that 1.8 and 1.4 times increase of ALT and trigliserid levels respectively caused a significant decrease in LAL activity. Reference range was determined to be 0.26-6.2 nmol/ml/hour, as being the same for males and females. Conclusion: No patient with KEDH diagnosis was determined. LAL lowness was found to show negative correlation with ALT, LDL-cholesterol and trigliserid. LAL lowness was found to be related to TBARS. The message to home: Dyslipidemia and /or transaminase elevation is together with LAL enzyme activity lowness in pediatric age group. Key words: lysosomal acid lipase, Wolman disease, cholesterol ester storage disease, chitotriosidase, CK-18, hsCRP, MPO, TBARS