Abstract | BACKGROUND: OBJECTIVE: DESIGN: 58 PKU subjects were provided 20 mg/kg of sapropterin for 1 month. Those who responded with at least a 15% decrease in plasma Phe received sapropterin for 1 year, while Non-responders discontinued it. After an additional 3 months, Responders who demonstrated increased Phe tolerance and decreased medical food dependence were classified as Definitive, whereas Responders unable to liberalize their diet without compromising plasma Phe control were identified as Provisional. At study visits, patients provided blood for plasma amino acids, 3-day diet records, and 12-hour urine samples analyzed for epinephrine (E), dopamine (DA), dihydroxyphenylacetate ( DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3MT), serotonin (5HT), and 5-hydroxyindole acetic acid (5HIAA) using HPLC with electrochemical detection. RESULTS: Compared with healthy non-PKU controls, subjects with PKU had significantly lower baseline concentrations of DA, HVA, 3MT, 5HT, and 5HIAA (p < 0.001 for all). Medical food protein intake had a direct association with DA, HVA, 5HT, and 5HIAA during the study (p < 0.05 for all), while plasma Phe had an inverse association with these markers (p < 0.01 for all). DOPAC was also associated with plasma Phe throughout the year (p = 0.035), although not at baseline. Patients with PKU had a significant increase in HVA (p = 0.015) after 1 month of sapropterin. When stratifying by Responder and Non-Responder status, significance of HVA increase in Non-responders (p = 0.041) was confirmed, but not in Responders (p = 0.081). A declining trend in urinary 5HIAA, significant only after controlling for plasma Phe (p = 0.019), occurred for Definitive Responders during the 1-year study. CONCLUSION:
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Authors | Teresa D Douglas, Hyder A Jinnah, Douglas Bernhard, Rani H Singh |
Journal | Molecular genetics and metabolism
(Mol Genet Metab)
Vol. 109
Issue 3
Pg. 243-50
(Jul 2013)
ISSN: 1096-7206 [Electronic] United States |
PMID | 23712020
(Publication Type: Journal Article)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- Amino Acids
- Biogenic Monoamines
- Neurotransmitter Agents
- Biopterin
- sapropterin
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Topics |
- Adolescent
- Adult
- Amino Acids
(blood)
- Biogenic Monoamines
(metabolism, urine)
- Biopterin
(analogs & derivatives, pharmacology)
- Case-Control Studies
- Child
- Child, Preschool
- Female
- Humans
- Male
- Metabolic Networks and Pathways
(drug effects)
- Neurotransmitter Agents
(metabolism)
- Phenylketonurias
(blood, metabolism, urine)
- Time Factors
- Young Adult
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