National Lysosomal Acid Lipase Deficiency Study
Condition: Cholesteryl Ester Storage Disease
MeSH terms: Cholesterol Ester Storage Disease; Wolman Disease; Metabolic Diseases
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients of 3 months to 18 years of age at the time of enrolment who have unexplained
        transaminase elevation (serum 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
      
Biospecimen description: 
      whole blood
    
Keywords: Cholesteryl Ester Storage Disease; Children; Liver disease