Andy De Souza (Presenter)
BC Children's Hospital
Authorship: Andy De Souza (1,2,3), Bojana Rakić (1,2,3), Hilary Vallance (1,2,3), Graham Sinclair (1,2,3)
(1) BC Children’s Hospital, Vancouver, BC (2) University of British Columbia, Vancouver, BC (3) Child and Family Research Institute, Vancouver, BC
The Newborn Screening Program at BC Children’s Hospital has diagnosed and confirmed 3 cases of MSUD since 2010. When stable, these patients are routinely monitored as outpatients, with plasma amino acid samples analyzed by the Biochemical Genetics Laboratory (BGL). BGL implemented TMS for plasma amino acid analysis in Spring 2014, switching from the widely used method of IEC coupled with post-column ninhydrin derivitization, a change that has improved testing capacity, reduced average turn-around-times, and streamlined laboratory workflows. In this presentation, we will demonstrate the impact that this method change has had on patient quality of care for acute admissions, using a case of an MSUD patient during an extended hospital stay for an acute decompensation event. Response times for “STAT” testing and the impact this had on immediate clinical management will be presented.
Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC). The treatment and management of patients with MSUD involves dietary restriction of protein, supplementation with amino acid mixtures free of branched chain amino acids (BCAA), and routine monitoring. Despite careful management, metabolic intoxication can occur. Triggers for acute metabolic decompensation include illness, dietary deviation, insufficient caloric intake, and injury. Acute metabolic decompensation for MSUD patients can be fatal and requires immediate treatment to minimize neurologic sequelae.
The Newborn Screening Program at BC Children’s Hospital has diagnosed and confirmed three cases of MSUD since 2010. When stable, these patients are routinely monitored as outpatients, with plasma amino acid samples analyzed by the Biochemical Genetics Laboratory (BGL). The most widely used method for amino acid analysis is ion-exchange chromatography coupled with post-column ninhydrin derivitization . This technique was utilized by BGL, but the combination of low throughput (maximum of eight samples a day) and increasing sample numbers (5% per year) led to a backlog and unacceptable turn-around-times. BGL implemented tandem mass spectrometry (TMS) for plasma amino acid analysis in Spring 2014, a change that has improved testing capacity, reduced average turn-around-times, and streamlined laboratory workflows.
In this presentation, we will demonstrate the impact that this method change has had on patient quality of care for acute admissions, using a case of an MSUD patient during an extended hospital stay for an acute decompensation event. Response times for “STAT” testing and the impact this had on immediate clinical management will be presented.
An MSUD patient was admitted to BC Children’s Hospital during an episode of acute metabolic decompensation triggered by an infection. The hospitalization lasted 18 days during which patient treatment included continuous renal replacement therapy, BCAA-free nutrition, and valine and isoleucine supplementation to promote protein anabolism. Appropriate clinical and laboratory assessments were performed to monitor and assess the stability of the patient. The plasma levels of leucine, isolecueine, alloisoleucine, and valine were determined by BGL using TMS. Blood samples were collected multiple times a day for STAT analysis of plasma BCAAs to determine the pattern of decompensation and, consequently, adjust treatment as necessary.
In MSUD patients, episodes of metabolic decompensation are emergency events; consequently, there is urgency for test results. In this presentation, we will take you through the timeline of STAT analyses performed by BGL, and compare the result times to theoretical responses from our previous methodology, as well as the impact these response times had on patient treatment. We will discuss the different scenarios encountered during this hospitalization period and our associated response times.
The TMS methodology employed by BGL has a turn-around-time of 112 minutes from start of sample preparation to completion of data acquisition under ideal conditions, including acquisition of a quality control. Comparatively, the timeline of the previous methodology was 260 minutes, without a quality control. TMS can deliver results 148 minutes faster than the Biochrom, therefore, adjustments to treatment can be made that much sooner, as was the scenario with this presented case. Furthermore, the increased testing capacity of TMS means we were able to test and report results for multiple STAT samples during laboratory hours, which we would be unable to do with our previous methodology, and which we will demonstrate. We also encountered a situation where we received a STAT request for another patient during this MSUD event, for which we will also demonstrate our improved performance with TMS.
With the incorporation of tandem mass spectrometry for amino acid analysis in the Biochemical Genetics Laboratory at BC Children’s Hospital, we have decreased our run-to-run time from 180 minutes on the Biochrom to 16 minutes by TMS. While this has had an impact on our 90th percentile average turn-around-times (212 days and rising with the Biochrom; 7 days with TMS), it is the response times for “STAT” testing, where there is an urgency for test results, and the impact on immediate clinical management where TMS has surpassed our previous methodology.
References & Acknowledgements:
 Spackman, D. H., Stein, W. H. Moore, S. (1958) Automatic recording apparatus for use in the chromatography of amino acids. Anal Chem 30, 1190–1206.
IP Royalty: no
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