a pilot study on diurnal variation

Conditions: Phenylketonuria (PKU)

Summary: this self-controlled, prospective, pilot study is designed to gather information regarding the diurnal variation (changes that occur each day) in the levels of plasma phenylalanine (phe) and tyrosine in patients with phenylketonuria (pku) and in the non-pku population.

phenylketonuria (pku) is a rare genetic metabolic disease caused by a mutation that codes for an enzyme that converts the essential amino acid phenylalanine (phe) into tyrosine. an absence or deficiency of this enzyme activity results in a phe elevation, where higher phe levels result in neurological damage. diurnal variations of phe levels have been observed in pku patients in a 24-hour period. as kuvan has shown to stabilize phe levels in pku patients over time, our hypothesis is that this can be demonstrated within a 24-hour period of observation and indicate therefore that kuvan may correlate with a lower plasma phe variability. this study on pku patients' diurnal variation will also provide important information as to the current method of blood phe monitoring in a clinical setting to learn more about the optimal way to measure phe concentration. the study will last about 4 weeks (6 study visits) for the pku participants and about 1 week (2 study visits) for the control group. participants will be required to follow a recommended diet, complete a dietary log, and undergo several blood draws, including a 24-hour blood assessment in which blood will be obtained 8 times throughout the day.

Eligibility criteria:
inclusion criteria: pku participants (arm 1): * subject has a confirmed diagnosis of pku with hyperphenylalaninemia documented by a fasting phenylalanine level of at least 360 umol/l (6 mg/dl) * patient is at least 4 years old (there is no upper age limit for this study) * willing and able to provide written authorization or, if under the age of 18 years, provide written assent (if required) and written patient authorization by a parent or legal guardian * willing to undergo study related procedures including commencing kuvan treatment for patient not currently on treatment; temporary discontinuation of kuvan for patient on treatment; and completing the 24-hour blood assessment * authorized to provide personal health information * subjects should not be pregnant and willing to use appropriate birth control during the study control group (arm 2): * healthy, non-pku individuals. they will be age-sex matched to the pku group. they may be a relative (ex: sibling) of a pku participant, but they don't have to be a blood relation. * individual is at least 4 years old (there is no upper age limit) * willing and able to provide written consent or, if under the age of 18 years, provide written assent and written participant authorization by a parent or legal guardian * authorized to provide personal health information exclusion criteria (both arms): * subjects who do not meet all the inclusion criteria * age \< 4 years * concomitant medical problems or medications which at the discretion of the principal investigator would put participant at health risk or prevent them from completing study. * if female, unwillingness to use birth control during the period of the study drug administration (this doesn't apply to arm 2)