L-Phenylalanine concentration in blood of phenylketonuria patients: a modified enzyme colorimetric assay compared with amino acid analysis, tandem mass spectrometry, and HPLC methods

Silva, Veronica De; Oldham, Charlie D.; May, Sheldon W.

doi:10.1515/cclm.2010.271

Cited by 24 publications

(23 citation statements)

References 37 publications

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“…The advantage is that the discussion on differences between measurement in blood spot versus plasma as shown in various articles is not of importance for this study. On the other hand, we do not know exactly how to translate our data and conclusions for measurements in plasma, knowing that the debate on the comparison between blood spot and plasma is ongoing (Gregory et al 2007;Kand'ár and Zakova 2009;De Silva et al 2010;Mo et al 2013;Groselj et al 2015).…”

Section: Methodological Issuesmentioning

confidence: 99%

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

et al. 2017

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Background: Treatment of hereditary tyrosinemia type 1 with nitisinone and phenylalanine and tyrosine restricted diet has largely improved outcome, but the best blood sampling time for assessment of metabolic control is not known. Aim: To study diurnal and day-to-day variation of phenylalanine and tyrosine concentrations in tyrosinemia type 1 patients. Methods: Eighteen tyrosinemia type 1 patients aged >1 year (median age 7.9 years; range 1.6-20.7) were studied. Capillary blood samples were collected 4 times a day (T1: pre-breakfast, T2: pre-midday meal, T3: before evening meal, and T4: bedtime) for 3 days. Linear mixed-effect models were used to investigate diurnal and day-to-day variation of both phenylalanine and tyrosine. Results: The coefficients of variation of phenylalanine and tyrosine concentrations were the lowest on T1 (13.8% and 14.1%, respectively). Tyrosine concentrations did not significantly differ between the different time points, but phenylalanine concentrations were significantly lower at T2 and T3 compared to T1 (50.1 mmol/L, 29.8 mmol/L, and 37.3 mmol/L, respectively). Conclusion: Our results indicated that for prevention of too low phenylalanine and too high tyrosine concentrations, measurement of phenylalanine and tyrosine pre-midday meal would be best, since phenylalanine concentrations are the lowest on that time point. Our results also indicated that whilst blood tyrosine concentrations were stable over 24 h, phenylalanine fluctuated. Day-to-day variation was most stable after an overnight fast for both phenylalanine and tyrosine. Therefore, in tyrosinemia type 1 patients the most reliable time point for measuring phenylalanine and tyrosine concentrations to enable interpretation of metabolic control is pre-breakfast.

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Section: Methodological Issuesmentioning

confidence: 99%

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

et al. 2017

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“…This will be accomplished by incorporation of a commercially available whole blood to plasma separation membrane that has been successfully demonstrated in devices by multiple groups (see ref. Given that the detection chemistry used in the paper-based Phe test has already been demonstrated to be compatible with Phe measurement from human blood samples in the clinically relevant range in the context of the laboratory-based ECA, 5 it is anticipated that the test will be compatible with clinical blood samples from PKU patients. The addition of the plasma membrane will increase both the input sample volume and the time to result for the test.…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7][8] Screening newborns at birth for elevated Phe has been demonstrated to be a cost-effective strategy to prevent the severe neurologic consequences of PKU, 9 however, the availability of newborn PKU screening varies greatly throughout the world. Phe testing for the diagnosis of phenylketonuria (PKU) in newborns is a classic example of goldstandard diagnostic assays being restricted to the high-resource laboratory setting.…”

Section: Introductionmentioning

confidence: 99%

Conversion of a laboratory-based test for phenylalanine detection to a simple paper-based format and implications for PKU screening in low-resource settings

Thiessen

Robinson

Reyes

et al. 2015

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Laboratory-based testing does not reach many individuals in lower-resource settings who could benefit from access to appropriate tests for diagnosis and therapy. A critical issue is laboratory-based testing often requires an environment with a high level of resources and supporting infrastructure that is not available in many areas of the world. The current report describes the conversion of a laboratory-based test for phenylalanine detection to a simple paper-based test appropriate for use in low-resource settings. The paper-based test is easy to operate, with all reagents stored dry on the card, is compatible with visible detection for clinically relevant concentrations of phenylalanine, and has a time to result of 10 minutes. Next steps for test development are discussed in the context of the potential for the paper-based Phe test to be used as a newborn PKU screening test in settings that are not well served by existing screening approaches.

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“…While the time from sample collection to result has decreased over time, and convenience has improved by allowing home collection of blood on filter paper spots with analysis by tandem mass spectrometry, the lag is still considerable and makes management of therapy based on real-time Phe levels impossible. Development of a home Phe meter, analogous to a home glucose meter, may ultimately resolve this issue [274].…”

Section: Emerging Technologies That Will Impact Treatment and Managemmentioning

confidence: 99%

Phenylketonuria Scientific Review Conference: State of the science and future research needs

Camp

Parisi

Acosta

et al. 2014

Molecular Genetics and Metabolism

212

158

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New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Confe...

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L-Phenylalanine concentration in blood of phenylketonuria patients: a modified enzyme colorimetric assay compared with amino acid analysis, tandem mass spectrometry, and HPLC methods

Abstract: The results reported here confirm that Phe concentrations determined by our ECA method are comparable to those determined by other widely used methods for a broad range of plasma Phe concentrations.

Cited by 24 publications

References 37 publications

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

Conversion of a laboratory-based test for phenylalanine detection to a simple paper-based format and implications for PKU screening in low-resource settings

Phenylketonuria Scientific Review Conference: State of the science and future research needs

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