title: Urinary metabolic profile of phenylketonuria in patients receiving total parenteral nutrition and medication.
abstract: Nutrition and drugs are main environmental factors that affect metabolism. We performed metabolomics of urine from an 8-year-old patient (case 1) with epilepsy and an 11-year-old patient (case 2) with malignant lymphoma who was being treated with methotrexate. Both patients were receiving total parenteral nutrition (TPN). We used our diagnostic procedure consisting of urease pretreatment, partial adoption of stable isotope dilution, gas chromatography/mass spectrometry (GC/MS) measurement and target analysis for 200 analytes including organic acids and amino acids. Surprisingly, their metabolic profiles were identical to that of phenylketonuria. The neopterin level was markedly above normal in case 1, and both neopterin and biopterin were significantly above normal in case 2. Mutation analysis of genomic DNA from case 1 showed neither homozygosity nor heterozygosity for phenylalanine hydroxylase deficiency. The metabolic profiles of both cases were normal when they were not receiving TPN. TPN is presently prohibited for individuals who have inherited disorders that affect amino acid metabolism. Although the Phe content of the TPN was not the sole cause of the PKU profile, its effect, combined with other factors, e.g. specific medication or possibly underlying diseases, led to this metabolic abnormality. The present study suggests that GC/MS-based metabolomics by target analysis could be important for assuring the safety of the treatments for patients receiving both TPN and methotrexate. Metabolomic profiling, both before and during TPN, is useful for determining the optimal nutritional formula not only for neonates, but also for young children who are known heterozygotes for metabolic disorders or whose status is unknown.
authors.affiliation: Division of Human Genetics, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. kuhara@kanazawa-med.ac.jp
authors.forename: Tomiko
authors.initials: T
authors.lastname: Kuhara
authors.forename: Morimasa
authors.initials: M
authors.lastname: Ohse
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Inoue
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shinka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Okano
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hongou
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Wakaba
authors.initials: W
authors.lastname: Morinobu
authors.forename: Hirosi
authors.initials: H
authors.lastname: Tamai
authors.forename: Kenji
authors.initials: K
authors.lastname: Omura
mesh_terms: D002648:Child; D002675:Child, Preschool; D006801:Humans; D008297:Male; D055442:Metabolome; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D010661:Phenylketonurias / Q000209:etiology* / Q000378:metabolism* / Q000652:urine; D014556:Urine / Q000737:chemistry*
chemical_list: D008727:Methotrexate