Cholesteryl Ester Storage Disease Clinical Trial
Official title:
The Frequency of Cholesteryl Ester Storage Disease in Children With Unexplained Transaminase Elevation and Chronic Liver Disease
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.
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