Estimation of undiagnosed lysosomal acid lipase deficiency in a paediatric population: a UK database study

Date of Approval: 
2016-07-20 00:00:00
Lay Summary: 
Lysosomal acid lipase deficiency (LAL-D) is a genetic condition in which production of the LAL enzyme is impaired. This enzyme is used to help break down fats in cells and when it is missing it means the fats are not broken down and instead accumulate in different organs of the body. LAL-D affects the liver and patients will often have elevated liver enzymes together with high levels of low density lipids (LDL) which are regarded as bad cholesterol and low levels of high density lipids (HDL) considered to be good cholesterol. It is thought that some patients with LAL-D are undiagnosed. In this study we wish to identify potential LAL-D patients aged between 2-18 within the Clinical Practice Research Datalink based upon test results indicating elevated liver enzymes and either elevated LDL or low HDL. We then wish to determine the potential number of undiagnosed LAL-D patients and to see which other medical conditions and treatments these patients have. To minimise the risk of patients being identified from the data sources all results relating to less than five patients will be supressed and broad categories used to summarise data.
Technical Summary: 
We aim to estimate the prevalence of undiagnosed Lysosomal acid lipase deficiency in a UK population based on the Clinical Practice Research Datalink and to tabulate the most commonly associated diagnoses and therapies. To achieve this we will use primary-care data from CPRD GOLD and secondary-care data from the linked Hospital Episode Statistics (HES). Patients (aged 2-18) will be identified based on either low density lipids > =130 mg/dL or High Density Lipids <40 mg/dL for males or <50mg/dL for females) and a test result for alanine transaminase > 1.5 x upper normal range occurring within +/-3 months of each other. Period prevalence will be calculated for 2014, using live patients registered within an up-to-standard (UTS) practice on the mid-year point (30th June 2014) as the denominator. Diagnoses and symptoms will be aggregated by Read code for CPRD GOLD data and ICD-10 codes for the HES dataset and presented in tabular format. Therapy codes will be aggregated by individual drug type and British National Formulary chapter and presented in tabular format. A sensitivity analysis based on patients eligible for the linkage scheme will also be performed. Findings will be summarised with wide granularity and all cells with n<5 suppressed in accordance with CPRD guidelines to prevent the risk of deductive/unintentional disclosure.
Health Outcomes to be Measured: 
The specific aim of the study is to identify a paediatric (2-18 years) population with both elevated low density lipids (LDL) and elevated alanine aminotransferase (ALT) in order to estimate a potentially undiagnosed population with LAL deficiency. We then wish to consider:. the prevalence of patients with these characteristics recorded diagnoses for this population therapies prescribed to this population
Application Number: 

Christopher Morgan - Chief Investigator - Pharmatelligence Limited
Alexander Cole - Collaborator - Alexion Pharmaceuticals
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited
Shona Fang - Collaborator - Alexion Pharmaceuticals

HES Admitted Patient Care