National Lysosomal Acid Lipase Deficiency Study

2015-03-04 00:23:23 | BioPortfolio


Cholesteryl Ester Storage Disease (CESD) is an autosomal recessive lysosomal storage disorder (LSD) caused by mutations in the lysosomal acid lipase gene (LIPA) that markedly reduce lysosomal acid lipase (LAL) activity, leading to the accumulation of lipids, predominately cholesteryl esters and triglycerides, in various tissues and cell types. In the liver, accumulation of lipids leads to diffuse microvesicular steatosis, which progresses to fibrosis and ultimately, to micronodular cirrhosis. Patients typically present with hepatomegaly, liver dysfunction, hepatic failure and type II hyperlipidemia. Although hepatosteatosis is a typical finding, the liver biopsy diagnosis may be misclassified as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis or cryptogenic liver disease. Biopsy and radiological findings are not considered diagnostic, but help to suspicion of CESD. The definitive diagnosis is based on deficient LAL activity and/or LIPA gene mutations.

CESD is pan-ethnic, however, the disease incidence is unknown. The estimated incidence of the disease indicates that CESD should be largely underdiagnosed especially in European patients. Elevation of serum transaminases, and hepatomegaly are early indications of liver impairment. Therefore, CESD should be considered as a differential diagnosis in liver disease of unknown origin.

To data, there is no study which evaluated the frequency of CESD in children with unexplained transaminase elevation and/or organomegaly and/or chronic liver disease. The aim of this prospective, multicenter and cross-sectional study is to investigate frequency of CESD in children with unexplained transaminase elevation and/or and/or chronic liver disease and to identify demographic and clinical features of CESD.


Patients of 3 months to 18 years of age at the time of enrolment who have unexplained transaminase elevation (serum alanine aminotransferase (ALT) levels > 1.5 times the upper limit of normal) for more than 3 months and/or unexplained hepatomegaly or hepatosplenomegaly and/or obesity- unrelated hepatosteatosis and/or biopsy-proven cryptogenic fibrosis and cirrhosis and/or liver transplantation for cryptogenic cirrhosis will be included.

Potential participants will be invited for LAL enzyme analysis. Written informed consent will be obtained from the parents or guardians of the participants at the time of enrolment. Prospective and retrospective data will be collected. Complete family and medical history, physical examination and previously existing laboratory findings will be recorded on standard case reports form and up to 0.25 ml of blood will be drawn for LAL enzyme analysis. The blood obtained from participants will be spotted on filter paper, and dried blood spot sample (DBS) will be prepared. Finally, the dried blood spot sample will be sent to reference laboratory (NHS Greater Glasgow and Clyde, England) for LAL enzyme measurement within 1 week.

Study Design

Observational Model: Cohort, Time Perspective: Prospective


Cholesteryl Ester Storage Disease


Ankara University School of Medicine




Ankara University

Results (where available)

View Results


Published on BioPortfolio: 2015-03-04T00:23:23-0500

Clinical Trials [234 Associated Clinical Trials listed on BioPortfolio]

Cholesterol Metabolism and Lipid Transfer in Diabetes

The diabetic dyslipidemia is one of the most important risk factor in the development of coronary artery disease. The low density lipoprotein (LDL)-like nanoemulsions is being used to stud...

Study of Glycogen Storage Disease and Associated Disorders

Glycogen, is the storage form of glucose. It is usually formed from sugar and stored in the liver. When tissues, such as muscle, need glucose for fuel the stored glycogen is converted in...

Study to Evaluate the Acute Bioavailability of EPA and DHA From a DietarySupplement in Healthy Men and Women

The objective of this study was to evaluate and compare the acute bioavailability of EPA and DHA in wax ester form provided as a dietary supplement compared to a well-studied and defined e...

International Registry Study of Neutral Lipid Storage Disease and Related Diseases

This study aims to understand the state of onset of NLSD(neutral lipid storage disease) / TGCV(triglyceride deposit cardiovasculopathy) worldwide, background information of affected patien...

Genetic Epidemiology of Lipoprotein-Lipid Levels

To determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors ...

PubMed Articles [17005 Associated PubMed Articles listed on BioPortfolio]

Cholesteryl ester storage disease: endoscopic findings of an orphan disease.

LIPA gene mutations affect the composition of lipoproteins: Enrichment in ACAT-derived cholesteryl esters.

Cholesteryl ester storage disease (CESD) due to LIPA gene mutations is characterized by hepatic steatosis, hypercholesterolemia and hypoalphalipoproteinemia, exposing affected patients to an increased...

Elevated cholesteryl ester transfer protein activity early in pregnancy predicts prediabetes 5 years later.

Cholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol levels and interaction between glucose and HDL metabolism is central in the development of diabetes.

OSBPL2 deficiency upregulate SQLE expression increasing intracellular cholesterol and cholesteryl ester by AMPK/SP1 and SREBF2 signalling pathway.

Previous studies have shown that oxysterol binding protein like 2 (OSBPL2) knockdown is closely related to cholesterol metabolism. However, whether there is a direct relation between OSBPL2 and choles...

Inhibition of cholesteryl ester synthesis by polyacetylenes from Atractylodes rhizome.

Using activity guided purification, four known compounds, sesquiterpene atractylenolide III (1), and the polyacetylenes 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol (2), 14-acetox...

Medical and Biotech [MESH] Definitions

The severe infantile form of inherited lysosomal lipid storage diseases due to deficiency of acid lipase (STEROL ESTERASE). It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes. It is also known as Wolman's xanthomatosis and is an allelic variant of CHOLESTEROL ESTER STORAGE DISEASE.

A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.

An autosomal recessive disorder caused by mutations in the gene for acid lipase (STEROL ESTERASE). It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes.

A hepatic GLYCOGEN STORAGE DISEASE in which there is an apparent deficiency of hepatic phosphorylase (GLYCOGEN PHOSPHORYLASE, LIVER FORM) activity.

An x-linked recessive hepatic glycogen storage disease resulting from lack of expression of phosphorylase-b-kinase activity. Symptoms are relatively mild; hepatomegaly, increased liver glycogen, and decreased leukocyte phosphorylase are present. Liver shrinkage occurs in response to glucagon.

More From BioPortfolio on "National Lysosomal Acid Lipase Deficiency Study"

Quick Search

Relevant Topic

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Searches Linking to this Trial