SSIEM 2016, Day 1: Opening ceremony with Prof Morava and Dr Rinaldo
SSIEM Day 1, including lecture highlights from Prof Eva Morava & Dr Piero Rinaldo
SSIEM 2016 opened with a rousing performance from a brass band to open our ears up ready to listen to the talks!
Prof Eva Morava: ‘Quo Vadis’, redefinition of inborn metabolic diseases, a challenge for the future.
(Professor of paediatrics in Tulane University at New Orleans and Editor-in-Chief of the Journal of Inherited Metabolic Disease)
Prof Morava discussed how the changing field of inborn errors of metabolism (IEM) research has unveiled new challenges as new disorders, new diagnostics and new treatments have emerged:
- Inherited metabolic disorders (IMD) used to be neatly categorised by the type of biochemical pathway involved e.g. disorders of breakdown, synthesis, storage etc. However, the discovery of several secondary metabolic disorders that manifest as IMD but are in fact not primary disorders of metabolism has complicated the classification and blurred the boundaries of IMDs. Prof Morava shared several examples of this.
- Next generation sequencing (NGS) has opened up the possibility of finding a diagnosis for challenging cases. However, Prof Morava noted that NGS is not perfect and often needs functional validation. Prof Morava gave illustrations of how ‘omic techniques such as glycomics, lipidomics and complexomics can be used.
- Over the past 20 years, there have been major changes in the therapies used in the IEM field with new treatments on the horizon.
The title of the talk posed the question to the IEM field ‘Quo vadis’ i.e. ‘where are you going?’ Prof Morava’s short answer was to go to infinity and beyond! Her longer answer was that she believes that the IEM research field has to envelope these new secondary disorders and not worry about redefining the IEM boundaries. Prof Morava believes that IEM researchers are primed to investigate these matters as clinical biochemical geneticists are exactly what is needed, along with their good collaborative skills and their creative approach to treatment and management options, including diet alterations.
Piero Rinaldo: New frontiers of neonatal screening.
(Mayo Clinic, Rochester, USA)
Dr Rinaldo shared with us his belief that to move diagnostic techniques forward in the IEM field we need collaboration in fair and transparent way. This is why he was involved in the development of the Region 4 stork (R4S) project which is an international collaborative newborn screening database containing tandem-mass spec data for 30 million normal newborns for use as control data alongside true-positive case data. It is hoped that this mass of data will help reduce the false positive rate of diagnostic testing.1,2
Since it’s inception, Dr Rinaldo’s goal has been to improve the way in which clinical validation is carried out. He believes that use of normal ranges and disease ranges in metabolomic tests are outdated and in their basic form shouldn’t be used because there is overlap between the two ranges and therefore the cutoff is arbitrary. Instead the Mayo clinic has developed the collaborative laboratory integrated results (CLIR) program that allows construction of four-dimensional reference ranges that can take account of patient age, birth weight, sex and location of testing centre. The programme also replaces analyte cut-offs with clinical significance thresholds and provides post analytical interpretive tools to integrate all relevant results into a single score. This is a password protected website tool that is freely available to anyone that contributes data to the project.3
As a take-home inspirational message, Dr Rinaldo proposed that the IEM field should aim to share even more data with a goal of 10 million reference profiles and 100 confirmed cases for every condition. He hopes we’ll be able to generate multidimensional reference thresholds and a 100:1 false positive ratio. As a cautionary tale, Dr Rinaldo shared that he was once asked by a funding body whether anyone was actually using the R4S tool and he realised he didn’t know the answer! He has since made sure he collects utilisation data: there have been 1.2 million page views.
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