120 - Familial Chylomicronaemia Syndrome: National Genetics Testing Results from the United Kingdom (ID 544)
Abstract
Background and Aims
Familial chylomicronaemia syndrome (FCS) is a rare disorder of lipid metabolism characterised by severe (>10mmol/L) fasting hypertriglyceridaemia and elevated circulating chylomicrons. MEDLINE and Embase literature searches established that only limited published data is available about genetic causes of FCS affecting the United Kingdom population. In this study, we aimed to provide the most comprehensive overview to date of FCS mutations identified within the United Kingdom.
Methods
We retrospectively reviewed the results of all specimens, received between November 2013 and June 2019, that requested genetic testing for FCS mutations (gene panel tested: lipoprotein lipase [LPL]; apolipoprotein C-II [APOC2]; glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 [GPIHBP1]; apolipoprotein A-V [APOA5]; lipase maturation factor 1 [LMF1]). Specimens that did not meet the sample acceptance policy, or those specimens yielding incomplete results, were excluded from further analysis. Patient demographics and genetic testing results were recorded, and the results were analysed using Microsoft Excel for Mac v16.3 (Microsoft; Washington, USA).
Results
273 patient specimens were tested. 108 patients were found to have pathogenic, likely pathogenic or variants of uncertain significance. Mutation and patient age distributions were as demonstrated (Figs. 1-2). Pathogenic or likely pathogenic variants were arranged hierarchically according to gene zygosity (Fig. 3).
Conclusions
To the best of our knowledge, this is the most comprehensive review to date of FCS mutations reported from the United Kingdom. Mutations in genes other than LPL appeared more common than expected, with a significant number of mutations identified in APOA5. The significant proportion of monoallelic mutations identified suggests a large manifesting heterozygote effect.
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