Parallel session
This session has been organised by the UK Metabolic Biochemistry Network (MetBioNet). The diagnosis and monitoring of inherited metabolic diseases (IMDs) is undergoing considerable change with the introduction of new genetic technologies, advances in treatments and discovery of biomarkers. This has resulted in diagnosis of more patients with IMDs and identification of new disorders but has also presented significant challenges to metabolic teams.
This session will start with an overview of current genetic technologies used in the diagnosis of IMD including rapid genomic investigations and the Generation Study and the challenges of interpretation of results. The development of biomarkers for lysosomal storage disorders (LSD) to help interpretation of genomic testing and for monitoring new treatments will be outlined in the second talk. The local team at the Manchester Centre for Genomic Medicine is internationally renowned for their clinical and diagnostic LSD services. We will finish with an overview of sitosterolaemia, one of the disorders increasingly being diagnosed by gene sequencing. Patients with this ultra-rare disorder are typically followed up in lipid clinics, however there are few patients in any centre and no national guidelines. This talk will share experience from the largest group of patients with the disorder in the UK.
Chair: Ann Bowron
9.30 Update on NHS Metabolic Genomics Services - Nicole Gossan
This talk will provide an overview of the genomic testing landscape for metabolic conditions in England, including whole genome sequencing (WGS), rapid exome and targeted panel testing. Testing strategies, results and limitations will be discussed.
10.00 The role of biomarkers in the diagnostic pathway of lysosomal disease - Heather Church
10.30 Clinical phenotype, diagnosis and management of sitosterolemia in adults - Elaine Murphy
Sitosterolemia is a rare autosomal recessive disorder of non-cholesterol sterol metabolism, caused by pathogenic variants of the ABCG5 or ABCG8 transporter genes. The function of the ABCG5 or ABCG8 transporter proteins is to limit intestinal absorption and promote biliary excretion of almost all of any absorbed plant phytosterols. When either of ABCG5 or ABCG8 are defective, this leads to hyperabsorption of sitosterol from the gastrointestinal tract and decreased biliary excretion, with accumulation of dietary phytosterols in different tissues.
Clinically the condition has a wide phenotype and is likely underdiagnosed. Alongside premature coronary artery disease, other features may include: xanthomas, abnormal liver function tests, arthralgia, splenomegaly, and haematological abnormalities.
As routine laboratory methods do not distinguish plant sterols from cholesterol (in the ‘lipid profile’), if sitosterolemia is not included in genetic panels of genes causing hypercholesterolemia then the condition can easily be missed.
Treatment includes a prescribed reduction of dietary sterols alongside medical management.
In this talk I will review the presentation, biochemistry, treatment and outcome of adult patients attending our unit, alongside a review of the current literature and management of sitosterolemia.
Heather studied Biology and Chemistry at Goldsmith’s College, University of London, graduating in 1987. She then gained a Ph.D. in analytical chemistry from the Department of Chemistry, University of Manchester in 1991. Heather worked as a post-doctoral research scientist within the Department of Obstetrics and Gynaecology, University of Manchester from 1991-1999 with a specific interest in cell adhesion and the role of extracellular matrix in human physiology.
In 1999 Heather took up the position of Clinical Biochemist in the Willink Biochemical Genetics Unit, now part of the Genomic Medicine, Manchester Foundation Trust with a specialist interest in lysosomal disease. Heather was appointed Principal Clinical Scientist in 2008 and has overseen the introduction of highly specialised laboratory services focussing on the improved diagnosis and monitoring treatment efficacy of pioneering new treatments for patients with lysosomal disease.
