title: Development of Metabolic Phenotype in Phenylketonuria: Evaluation of the Blaskovics Protein Loading Test at 5 Years of Age.
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 m2body surface and day) of 2-hydroxyphenylacetic acid was increased 1.9-fold (P < 0.01). Corresponding with these analytical data, the kinetic model constant koutof 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.
  
  
  CONCLUSIONS
  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.affiliation: Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Burgard
authors.affiliation: Charité Universitätsmedizin Berlin, CampusVirchow-Klinikum, CC13, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Mönch
authors.affiliation: Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Zschocke
authors.affiliation: Children's Hospital, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Wendel
authors.affiliation: Institute of Human Genetics, Frankfurt University Hospital, Frankfurt/Main, Germany. ulrich.langenbeck@gmx.net.
authors.forename: U
authors.initials: U
authors.lastname: Langenbeck