Blood phenylalanine monitoring for dietary compliance among patients with phenylketonuria: comparison of methods

Gregory, Cria O.; Yu, Chunli; Singh, Rani H.

doi:10.1097/gim.0b013e318159a355

Cited by 46 publications

(57 citation statements)

References 17 publications

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“…The measure of PHE levels in blood varies dependent on the analytical method used; therefore, consistency of testing methodology is important for comparison over time. 32 Newly diagnosed infants should be seen in clinic frequently with PHE and TYR testing until the PHE levels are stabilized. Subsequently, blood PHE levels should be monitored at least weekly until age 1 with increased surveillance during periods of rapid growth and transitions of diet, such as with the introduction of solid foods.…”

Section: Goals and Monitoring Of Therapymentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

540

443

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Phenylalanine hydroxylase (PAH) deficiency, traditionally called phenylketonuria (PKU) due to characteristic phenylketones accumulating in the urine of affected individuals, has a significant place in history as the first inborn error of metabolism identified through population-based screening, initiating a new era in the diagnosis and treatment of genetic disorders. PKU was first described in 1934 by the Norwegian physician Asbjörn Fölling, but it was not until the mid-1950s that a patient with PAH deficiency was treated with a low phenylalanine (PHE) diet. Although this first patient already had irreversible Phenylalanine hydroxylase deficiency, traditionally known as phenylketonuria, results in the accumulation of phenylalanine in the blood of affected individuals and was the first inborn error of metabolism to be identified through population screening. Early identification and treatment prevent the most dramatic clinical sequelae of the disorder, but new neurodevelopmental and psychological problems have emerged in individuals treated from birth. The additional unanticipated recognition of a toxic effect of elevated maternal phenylalanine on fetal development has added to a general call in the field for treatment for life. Two major conferences sponsored by the National Institutes of Health held >10 years apart reviewed the state of knowledge in the field of phenylalanine hydroxylase deficiency, but there are no generally accepted recommendations for therapy. The purpose of this guideline is to review the strength of the medical literature relative to the treatment of phenylalanine hydroxylase deficiency and to develop recommendations for diagnosis and therapy of this disorder. Evidence review from the original National Institutes of Health consensus conference and a recent update by the Agency for Healthcare Research and Quality was used to address key questions in the diagnosis and treatment of phenylalanine hydroxylase deficiency by a working group established by the American College of Medical Genetics and Genomics. The group met by phone and in person over the course of a year to review these reports, develop recommendations, and identify key gaps in our knowledge of this disorder.Above all, treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenylalanine in the range of 120-360 µmol/l. Treatment has predominantly been dietary manipulation, and use of low protein and phenylalanine medical foods is likely to remain a major component of therapy for the immediate future. Pharmacotherapy for phenylalanine hydroxylase deficiency is in early stages with one approved medication (sapropterin, a derivative of the natural cofactor of phenylalanine hydroxylase) and others under development. Eventually, treatment of phenylalanine hydroxylase deficiency will be individualized with multiple medications and alternative medical foods available to tailor therapy. The primary goal of therapy should be to lower blood phenylalanine, and any interventions, including medica...

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Section: Goals and Monitoring Of Therapymentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

540

443

View full text Add to dashboard Cite

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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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“…In addition, the blood Phe/Tyr level ratio is lately recognized as a sensitive indicator of metabolic control in patients with HPA where the increased ratios are shown to be associated with cognitive deficits, perhaps even more strongly than increased Phe levels alone [10][11][12]. Thus, the dietary treatment of patients with HPA goes along with regular monitoring of the Phe and the Tyr levels, where the method of choice needs to be as accurate, simple, rapid and cheap as possible [13]. Guidelines and recommendations on management patients with HPA propose serial monitoring of blood Phe levels weekly in infants and toddlers and later on monthly at least in pre-pubertal children [7].…”

Section: Introductionmentioning

confidence: 96%

“…However, the precise cause is not elucidated [13,17,18]. Furthermore, scarce data exist on comparisons of the methods for measuring the Tyr levels [18].…”

Section: Introductionmentioning

confidence: 98%