Diurnal Variations of Serum Phenylalanine in Phenylketonuric Children on Low Phenylalanine Diet

Güttler, Flemming; Olesen, E. S.; Wamberg, E

doi:10.1093/ajcn/22.12.1568

Cited by 29 publications

(18 citation statements)

References 2 publications

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“…Blood Phe and tyrosine have diurnal variation, so blood drawing needs to be done at similar times. 48 Most of the mutations tested in this study have been reported in earlier BH 4 trials. 31,49 -50 However, five previously unreported mutations have been found to be BH 4 responsive.…”

Section: Discussionmentioning

confidence: 99%

Biopterin responsive phenylalanine hydroxylase deficiency

Matalon

Koch

Michals‐Matalon

et al. 2004

Genetics in Medicine

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Purpose: Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene. There have been more than 400 mutations identified in the PAH gene leading to variable degrees of deficiency in PAH activity, and consequently a wide spectrum of clinical severity. A pilot study was undertaken to examine the response to 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH 4 ) in patients with atypical and classical PKU. Methods: PAH gene mutation analysis was performed using denaturing gradient gel electrophoresis and gene sequencing. Patients with classical, atypical, or mild PKU were orally given BH4 10 mg/kg. Blood phenylalanine and tyrosine levels were determined using tandem MS/MS at 0 hours, 4 hours, 8 hours, and 24 hours intervals. Results: Thirty-six patients were given a single oral dose of 10 mg/kg of BH 4 . Twenty one patients (58.33%) responded with a decrease in blood phenylalanine level. Of the patients that responded, 12 were classical, 7 atypical, and 2 mild. The mean decline in blood phenylalanine at 24 hours was Ͼ 30% of baseline.There were 15 patients who did not respond to the BH 4 challenge, 14 of those had classical and one had atypical PKU. Mapping the mutations that responded to BH 4 on the PAH enzyme showed that mutations were in the catalytic, regulatory, oligomerization, and BH 4 binding domains. Five patients responding to BH 4 had mutations not previously identified. Conclusion: The data presented suggest higher than anticipated number of PKU mutations respond to BH 4 , and such mutations are on all the domains of PAH. Genet Med 2004:6(1):27-32.

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Section: Discussionmentioning

confidence: 99%

Biopterin responsive phenylalanine hydroxylase deficiency

Matalon

Koch

Michals‐Matalon

et al. 2004

Genetics in Medicine

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“…For clinical practice it seems reasonable to recommend an average compliance within the boundaries of the target values for Phe control. Possible adverse outcome eects of extremely low blood Phe levels have been debated for some time [21,22,39,70]. In data from the British Phenylketonuria Register [70].…”

Section: Lower Target Value For Blood Phenylalanine Level Concentrationsmentioning

confidence: 99%

“…The authors concluded that the timing of blood sampling is not a signi®cant factor for the monitoring of PKU treatment. GuÈ ttler et al [21] have suggested that an overnight rise in Phe levels in PKU patients could be due to net protein catabolism and release of Phe into the plasma amino acid pool. However, when protein anabolism during the day is predominating (as in healthy children) children should thrive well.…”

Section: Lower Target Value For Blood Phenylalanine Level Concentrationsmentioning

confidence: 99%

Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997

Burgard

Bremer

Bührdel

et al. 1999

European Journal of Pediatrics

129

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“…Therefore, the magnitude of the Phe load was adapted to the individual Phe tolerance. Furthermore, sampling time was set before breakfast, thus preventing differences in blood Phe concentrations due to diurnal variations, as shown in previous studies [5,6,7,9]. …”

Section: Discussionmentioning

confidence: 99%

“…Studies on the variation of blood Phe concentrations have examined changes occurring within 24 h [5,6,7,8,9]; however, variation in timing and frequency of blood sampling warrant further scrutiny. The advised frequency of blood sampling decreases with age (van Spronsen, personal communication, Dutch guidelines) [10], but knowledge of individual variations in day-to-day and week-to-week blood Phe concentrations, together with the effects of changes in Phe intake in adolescence and adulthood, is scarce.…”

Section: Introductionmentioning

confidence: 99%

Adult Patients with Well-Controlled Phenylketonuria Tolerate Incidental Additional Intake of Phenylalanine

Rijn¹,

Hoeksma²,

Sauer³

et al. 2011

Ann Nutr Metab

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Background/Aims: In patients with phenylketonuria (PKU), target ranges of blood phenylalanine (Phe) concentrations have been tightened in order to improve long-term outcomes. We investigated day-to-day and week-to-week variations in blood Phe concentration and the effect of an additional Phe load. Methods: We performed a longitudinal study in 6 adult PKU patients. The study was divided in five 7-day periods: 1 period without any intervention (period I) and 4 periods with a Phe load on day 3 equivalent to 100% (periods II and III) and to 200% (periods IV and V) of each patient’s individual daily Phe intake. Phe loading was given as encapsulated L-Phe. Blood spots to measure blood Phe concentration were taken each morning before breakfast in all periods. Results: Day-to-day and week-to-week blood Phe concentrations varied considerably with and without intervention in Phe intake. Equal loads of Phe did not result in comparable effects in blood Phe concentrations in all patients. In periods II–IV, mean blood Phe concentrations of days 1–3 (pre-load) were not significantly different from days 4–7 (post-load). The 200% load resulted in a significantly larger variation. Conclusion: These results showed that patients with well-controlled PKU can incidentally tolerate 100% – and in some cases 200% – of their normal daily Phe intake.

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Diurnal Variations of Serum Phenylalanine in Phenylketonuric Children on Low Phenylalanine Diet

Cited by 29 publications

References 2 publications

Biopterin responsive phenylalanine hydroxylase deficiency

Biopterin responsive phenylalanine hydroxylase deficiency

Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997

Adult Patients with Well-Controlled Phenylketonuria Tolerate Incidental Additional Intake of Phenylalanine

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