P Burgard1, E Mönch2, J Zschocke3, U Wendel4, U Langenbeck5. 1. Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany. 2. Charité Universitätsmedizin Berlin, CampusVirchow-Klinikum, CC13, Berlin, Germany. 3. Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria. 4. Children's Hospital, University of Düsseldorf, Düsseldorf, Germany. 5. Institute of Human Genetics, Frankfurt University Hospital, Frankfurt/Main, Germany. ulrich.langenbeck@gmx.net.
Abstract
BACKGROUND: As part of the German Collaborative Study on Phenylketonuria (PKU)/Hyperphenylalaninaemia (HPA) Study Protocol, a Blaskovics protein loading test (180 mg phenylalanine (phe) protein equivalent per kg body weight and day for 72 h) had been applied to 145 children at the age of 6 months. For investigating possible age-related changes of metabolic phenotype, 51 of them received a 2nd loading test at 5 years of age. METHODS: Besides the analysis of blood phe levels, acidic phe transamination metabolites were quantified in urine. RESULTS: Compared to the 6-month data, the mean blood phe level 72 h after start of loading (Phe72) was found to be decreased by 7% (P = 0.06), whereas the mean urinary excretion (per 1.73 m2 body surface and day) of 2-hydroxyphenylacetic acid was increased 1.9-fold (P < 0.01). Corresponding with these analytical data, the kinetic model constant k out of metabolic plus renal phe disposal was found increased 1.3-fold in mean (P < 0.01).In 3 of the 51 patients, Phe72 was very high at 6 months while in the medium range at 5 years, suggesting that catabolic states may mimic a more severe metabolic defect.The blood phe level response of mild PKU (type II) was assigned identically at both ages in 7/9 patients. Diverging results were (i) response type III (mild hyperphenylalaninaemia) at 6 months and type II at 5 years and (ii) type II at 6 months and type III at age 5. CONCLUSION: Renal elimination of OHPAA and phe tolerance increase significantly between the age of 6 months and 5 years, suggesting that, at least in childhood, formation and/or renal disposal of phe transamination metabolites may be major distal determinants of phe tolerance.
BACKGROUND: As part of the German Collaborative Study on Phenylketonuria (PKU)/Hyperphenylalaninaemia (HPA) Study Protocol, a Blaskovics protein loading test (180 mg phenylalanine (phe) protein equivalent per kg body weight and day for 72 h) had been applied to 145 children at the age of 6 months. For investigating possible age-related changes of metabolic phenotype, 51 of them received a 2nd loading test at 5 years of age. METHODS: Besides the analysis of blood phe levels, acidic phe transamination metabolites were quantified in urine. RESULTS: Compared to the 6-month data, the mean blood phe level 72 h after start of loading (Phe72) was found to be decreased by 7% (P = 0.06), whereas the mean urinary excretion (per 1.73 m2 body surface and day) of 2-hydroxyphenylacetic acid was increased 1.9-fold (P < 0.01). Corresponding with these analytical data, the kinetic model constant k out of metabolic plus renal phe disposal was found increased 1.3-fold in mean (P < 0.01).In 3 of the 51 patients, Phe72 was very high at 6 months while in the medium range at 5 years, suggesting that catabolic states may mimic a more severe metabolic defect.The blood phe level response of mild PKU (type II) was assigned identically at both ages in 7/9 patients. Diverging results were (i) response type III (mild hyperphenylalaninaemia) at 6 months and type II at 5 years and (ii) type II at 6 months and type III at age 5. CONCLUSION: Renal elimination of OHPAA and phe tolerance increase significantly between the age of 6 months and 5 years, suggesting that, at least in childhood, formation and/or renal disposal of phe transamination metabolites may be major distal determinants of phe tolerance.
Authors: Y Okano; R C Eisensmith; F Güttler; U Lichter-Konecki; D S Konecki; F K Trefz; M Dasovich; T Wang; K Henriksen; H Lou Journal: N Engl J Med Date: 1991-05-02 Impact factor: 91.245
Authors: F J van Spronsen; M van Rijn; B Dorgelo; M Hoeksma; A M Bosch; M F Mulder; J B C de Klerk; T de Koning; M Estela Rubio-Gozalbo; M de Vries; P H Verkerk Journal: J Inherit Metab Dis Date: 2009-01-10 Impact factor: 4.982