1. Patients with classical PKU phenotype (serum phenylalanine concentration > 10 mg/dL on a normal diet at diagnosis) # ~25
2. Patients with hyperphenylalaninemia (serum phenylalanine concentration < 10 mg/dL on a normal diet at diagnosis) # ~15
3. Patients with PKU on therapy with Kuvan # ~10

Study Controls: Up to 50 children and adults without a known metabolic disorder.

Skin sample collection: samples of human stratum corneum will be obtained with squame adhesive tape disks typically at the time of their clinic appointment. The tape will be placed on the inside of the forearm and the procedure will be repeated up to five times per patient to have sufficient corneocytes for analysis. This type of sampling is non-invasive.

The establishment of normative data for the skin metabolome will provide a baseline for assessing changes in the skin metabolome that occur during development and with disease.

By exhaustive extraction of the adhesive tapes with organic solvents, the investigators will analyze the metabolome of the stratum corneum with developed targeted methods for amino acids. The analysis will be performed using ultra high performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLCQTOF-MS) to identify biochemical changes in the tape-stripped skin metabolome. With the comparative intensity/concentration results of identified metabolites, a subsequent metabolic network reconstruction will be carried out to reveal the underlying mechanism perturbed in PKU and metabolic response to diet or therapeutic interventions.

By exhaustive extraction of the adhesive tapes with organic solvents, the investigators will analyze the metabolome of the stratum corneum with developed targeted methods for amino acids. The analysis will be performed using ultra high performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLCQTOF-MS) to identify biochemical changes in the tape-stripped skin metabolome. With the comparative intensity/concentration results of identified metabolites, a subsequent metabolic network reconstruction will be carried out to reveal the underlying mechanism perturbed in PKU and metabolic response to diet or therapeutic interventions.

Determine if the metabolomic profile changes over time in patients with PKU. By exhaustive extraction of the adhesive tapes with organic solvents, the investigators will analyze the metabolome of the stratum corneum with developed targeted methods for amino acids. The analysis will be performed using ultra high performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLCQTOF-MS) to identify biochemical changes in the tape-stripped skin metabolome. With the comparative intensity/concentration results of identified metabolites, a subsequent metabolic network reconstruction will be carried out to reveal the underlying mechanism perturbed in PKU and metabolic response to diet or therapeutic interventions.