National Lysosomal Acid Lipase Deficiency Study (LAL-D)
|ClinicalTrials.gov Identifier: NCT02372513|
Recruitment Status : Completed
First Posted : February 26, 2015
Last Update Posted : November 13, 2017
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.
|Condition or disease|
|Cholesteryl Ester Storage Disease|
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 Type :||Observational|
|Actual Enrollment :||810 participants|
|Official Title:||The Frequency of Cholesteryl Ester Storage Disease in Children With Unexplained Transaminase Elevation and Chronic Liver Disease|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||January 31, 2017|
|Actual Study Completion Date :||March 1, 2017|
- Frequency of Cholesteryl Ester Storage Disease in children who have unexplained transaminase elevation for more than 3 months and/or organomegaly and/or hepatosteatosis unrelated to obesity and/or cryptogenic fibrosis and cirrhosis [ Time Frame: First day ]
- Identify demographic and clinical features of Cholesteryl Ester Storage Disease [ Time Frame: First day ]
Biospecimen Retention: Samples Without DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02372513
|Ankara University School of Medicine|
|Study Director:||Zarife Kuloglu, M.D||Ankara University School of Medicine|