Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control

M Lindner; G Gramer; S F Garbade; P Burgard

doi:10.1007/s10545-009-1070-7

Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin

Standard

Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin : assessing responsiveness in a model of statistical process control. / Lindner, M; Gramer, G; Garbade, S F; Burgard, P.

In: J INHERIT METAB DIS, Vol. 32, No. 4, 08.2009, p. 514-22.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lindner, M, Gramer, G, Garbade, SF & Burgard, P 2009, 'Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control', J INHERIT METAB DIS, vol. 32, no. 4, pp. 514-22. https://doi.org/10.1007/s10545-009-1070-7

APA

Lindner, M., Gramer, G., Garbade, S. F., & Burgard, P. (2009). Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control. J INHERIT METAB DIS, 32(4), 514-22. https://doi.org/10.1007/s10545-009-1070-7

Vancouver

Lindner M, Gramer G, Garbade SF, Burgard P. Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control. J INHERIT METAB DIS. 2009 Aug;32(4):514-22. https://doi.org/10.1007/s10545-009-1070-7

Bibtex

@article{cede6ee4cd5e428da9c5cbeead260a60,

title = "Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control",

abstract = "Tetrahydrobiopterin (BH(4)) cofactor loading is a standard procedure to differentiate defects of BH(4) metabolism from phenylalanine hydroxylase (PAH) deficiency. BH(4) responsiveness also exists in PAH-deficient patients with high residual PAH activity. Unexpectedly, single cases with presumed nil residual PAH activity have been reported to be BH(4) responsive, too. BH(4) responsiveness has been defined either by a >or=30% reduction of blood Phe concentration after a single BH(4) dose or by a decline greater than the individual circadian Phe level variation. Since both methods have methodological disadvantages, we present a model of statistical process control (SPC) to assess BH(4) responsiveness. Phe levels in 17 adult PKU patients of three phenotypic groups off diet were compared without and with three different single oral dosages of BH(4) applied in a double-blind randomized cross-over design. Results are compared for >or=30% reduction and SPC. The effect of BH(4) by >or=30% reduction was significant for groups (p < 0.01) but not for dose (p = 0.064), with no interaction of group with dose (p = 0.24). SPC revealed significant effects for group (p < 0.01) and the interaction for group with dose (p < 0.05) but not for dose alone (p = 0.87). After one or more loadings, seven patients would be judged to be BH(4) responsive either by the 30% criterion or by the SPC model, but only three by both. Results for patients with identical PAH genotype were not very consistent within (for different BH(4) doses) and between the two models. We conclude that a comparison of protein loadings without and with BH(4) combined with a standardized procedure for data analysis and decision would increase the reliability of diagnostic results.",

keywords = "Administration, Oral, Adult, Biopterin/adverse effects, Cross-Over Studies, Diet, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Models, Statistical, Phenylalanine/blood, Phenylalanine Hydroxylase/deficiency, Phenylketonurias/blood, Treatment Outcome, Young Adult",

author = "M Lindner and G Gramer and Garbade, {S F} and P Burgard",

year = "2009",

month = aug,

doi = "10.1007/s10545-009-1070-7",

language = "English",

volume = "32",

pages = "514--22",

journal = "J INHERIT METAB DIS",

issn = "0141-8955",

publisher = "Springer Netherlands",

number = "4",

}

RIS

TY - JOUR

T1 - Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin

T2 - assessing responsiveness in a model of statistical process control

AU - Lindner, M

AU - Gramer, G

AU - Garbade, S F

AU - Burgard, P

PY - 2009/8

Y1 - 2009/8

N2 - Tetrahydrobiopterin (BH(4)) cofactor loading is a standard procedure to differentiate defects of BH(4) metabolism from phenylalanine hydroxylase (PAH) deficiency. BH(4) responsiveness also exists in PAH-deficient patients with high residual PAH activity. Unexpectedly, single cases with presumed nil residual PAH activity have been reported to be BH(4) responsive, too. BH(4) responsiveness has been defined either by a >or=30% reduction of blood Phe concentration after a single BH(4) dose or by a decline greater than the individual circadian Phe level variation. Since both methods have methodological disadvantages, we present a model of statistical process control (SPC) to assess BH(4) responsiveness. Phe levels in 17 adult PKU patients of three phenotypic groups off diet were compared without and with three different single oral dosages of BH(4) applied in a double-blind randomized cross-over design. Results are compared for >or=30% reduction and SPC. The effect of BH(4) by >or=30% reduction was significant for groups (p < 0.01) but not for dose (p = 0.064), with no interaction of group with dose (p = 0.24). SPC revealed significant effects for group (p < 0.01) and the interaction for group with dose (p < 0.05) but not for dose alone (p = 0.87). After one or more loadings, seven patients would be judged to be BH(4) responsive either by the 30% criterion or by the SPC model, but only three by both. Results for patients with identical PAH genotype were not very consistent within (for different BH(4) doses) and between the two models. We conclude that a comparison of protein loadings without and with BH(4) combined with a standardized procedure for data analysis and decision would increase the reliability of diagnostic results.

AB - Tetrahydrobiopterin (BH(4)) cofactor loading is a standard procedure to differentiate defects of BH(4) metabolism from phenylalanine hydroxylase (PAH) deficiency. BH(4) responsiveness also exists in PAH-deficient patients with high residual PAH activity. Unexpectedly, single cases with presumed nil residual PAH activity have been reported to be BH(4) responsive, too. BH(4) responsiveness has been defined either by a >or=30% reduction of blood Phe concentration after a single BH(4) dose or by a decline greater than the individual circadian Phe level variation. Since both methods have methodological disadvantages, we present a model of statistical process control (SPC) to assess BH(4) responsiveness. Phe levels in 17 adult PKU patients of three phenotypic groups off diet were compared without and with three different single oral dosages of BH(4) applied in a double-blind randomized cross-over design. Results are compared for >or=30% reduction and SPC. The effect of BH(4) by >or=30% reduction was significant for groups (p < 0.01) but not for dose (p = 0.064), with no interaction of group with dose (p = 0.24). SPC revealed significant effects for group (p < 0.01) and the interaction for group with dose (p < 0.05) but not for dose alone (p = 0.87). After one or more loadings, seven patients would be judged to be BH(4) responsive either by the 30% criterion or by the SPC model, but only three by both. Results for patients with identical PAH genotype were not very consistent within (for different BH(4) doses) and between the two models. We conclude that a comparison of protein loadings without and with BH(4) combined with a standardized procedure for data analysis and decision would increase the reliability of diagnostic results.

KW - Administration, Oral

KW - Adult

KW - Biopterin/adverse effects

KW - Cross-Over Studies

KW - Diet

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Male

KW - Models, Statistical

KW - Phenylalanine/blood

KW - Phenylalanine Hydroxylase/deficiency

KW - Phenylketonurias/blood

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1007/s10545-009-1070-7

DO - 10.1007/s10545-009-1070-7

M3 - SCORING: Journal article

C2 - 19513811

VL - 32

SP - 514

EP - 522

JO - J INHERIT METAB DIS

JF - J INHERIT METAB DIS

SN - 0141-8955

IS - 4

ER -