Diurnal variation of phenylalanine concentrations in tyrosinaemia type 1: should we be concerned?

Daly, Anne; Gökmen-Özel, H.; MacDonald, Anita; Preece, MA; Davies, P.H. O'Connor; Chakrapani, Anupam; McKiernan, Patrick

doi:10.1111/j.1365-277x.2011.01215.x

Cited by 25 publications

(48 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, blood phenylalanine concentrations in HT1 have previously been reported to show a large diurnal variation, consistently being lower in the afternoon (Daly et al 2012), while previous reports showed that detection of deficient intake of essential amino acids can best be detected by comparing an overnight fasting and postprandial blood sample (Ozalp et al 1972). Further studies may therefore best include a differential overnight fasting to postprandial measurement.…”

Section: Discussionmentioning

confidence: 97%

“…Therefore, tyrosine intake is limited by severe natural protein restriction and supplementation of a synthetic amino acid mixture devoid of tyrosine and phenylalanine, as tyrosine is primarily derived from hydroxylation of dietary phenylalanine. This results in both high tyrosine and low phenylalanine concentrations (De Laet et al 2011;Daly et al 2012;Wilson et al 2000), with dietary treatment being primarily monitored based on tyrosine concentrations. In phenylketonuria, too strict dietary treatment, resulting in "low" phenylalanine concentrations, has shown to be related to impaired growth and development (Teissier et al 2012;Rouse 1966;Smith et al 1990;Pode-Shakked et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…In tyrosinemia type II, high tyrosine concentrations are associated with mental retardation. Together, this raises the question whether current dietary treatment creates a tyrosine toxicity or a phenylalanine deficiency that may impair growth and brain development (De Laet et al 2011;Daly et al 2012;Wilson et al 2000) and whether phenylalanine supplementation is beneficial or only increases tyrosine concentrations (Daly et al 2012;Wilson et al 2000).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Infants with Tyrosinemia Type 1: Should phenylalanine be supplemented?

et al. 2014

View full text Add to dashboard Cite

Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism caused by fumarylacetoacetase deficiency. Biochemically, this results in accumulation of toxic metabolites including succinylacetone. Clinically, HT1 is characterized by severe liver, kidney, and neurological problems. Treatment with NTBC and dietary restriction of tyrosine and phenylalanine have strongly improved outcome, but impaired neurocognitive development has been reported. Whether impaired neurocognitive outcome results from high blood tyrosine or low blood phenylalanine concentrations is currently unknown. In this report, two HT1 newborns, diagnosed by neonatal screening, are presented. The first patient showed low phenylalanine concentrations, growth retardation, neurological impairments, and skin problems, clearly improving after institution of phenylalanine supplementation (~30 mg/kg/ day) at age 6 months, while both blood phenylalanine and tyrosine concentrations increased. In the second patient, phenylalanine supplementation (~20 mg/kg/day) was initiated as soon as low phenylalanine concentrations were observed at age 19 days. On this regimen, blood phenylalanine concentrations increased, and hypophenylalaninemia was less frequently observed than in the first patient, whereas blood tyrosine concentrations tended to increase. Clinically, no growth, neurological, or skin problems have been observed. The combination of knowledge obtained from these cases suggests that hypophenylalaninemia rather than hypertyrosinemia during the first months of life may impair neurocognitive development in young HT1 infants. Phenylalanine supplementation should really be considered in HT1 patients with consistently low blood phenylalanine concentrations during the first months of life. However, the minimal phenylalanine concentrations acceptable and the optimal phenylalanine supplementation regimen require further investigation.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Infants with Tyrosinemia Type 1: Should phenylalanine be supplemented?

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Two studies have paid attention to the variation of phenylalanine and tyrosine concentrations in HT1 patients (Wilson et al 2000;Daly et al 2012). The first was an intervention study in five HT1 patients and one tyrosinemia type II patient showing that phenylalanine concentrations decreased during the day in five patients (Wilson et al 2000).…”

Section: Introductionmentioning

confidence: 99%

“…The first was an intervention study in five HT1 patients and one tyrosinemia type II patient showing that phenylalanine concentrations decreased during the day in five patients (Wilson et al 2000). The second study was a retrospective study in eleven HT1 patients showing lower blood phenylalanine concentrations in the afternoon (Daly et al 2012). Notwithstanding of clear interest, these studies leave the predictability of a single blood sample of phenylalanine and tyrosine in a 24 h time period and from day-to-day to be studied.…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract