title: Tyrosine monitoring in children with early and continuously treated phenylketonuria: results of an international practice survey.
abstract: Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly associated with EF deficit than phe alone. A high phe:tyr ratio is hypothesized to lead to a reduction in dopamine synthesis within the brain, which in turn results in the development of EF impairment. This paper provides a snapshot of current practice in the monitoring and/or treatment of tyrosine levels in children with PKU, across 12 countries from Australasia, North America and Europe. Tyrosine monitoring in this population has increased over the last 5 years, with over 80% of clinics surveyed reporting routine monitoring of tyrosine levels in infancy alongside phe levels. Twenty-five percent of clinics surveyed reported actively treating/managing tyrosine levels (with supplemental tyrosine above that contained in PKU formulas) to ensure tyrosine levels remain within normal ranges. Anecdotally, supplemental tyrosine has been reported to ameliorate symptoms of both attention deficit hyperactivity disorder and depression in this population. EF assessment of children with ECT-PKU was likewise highly variable, with 50% of clinics surveyed reporting routine assessments of intellectual function. However when function was assessed, test instruments chosen tended towards global measures of IQ prior to school entry, rather than specific assessment of EF development. Further investigation of the role of tyrosine and its relationship with phe and EF development is needed to establish whether routine tyrosine monitoring and increased supplementation is recommended.
authors.affiliation: School of Psychology and Counselling, Queensland University of Technology, PO Box 2434, QLD 4001, Queensland, Australia. r.sharman@qut.edu.au
authors.forename: Rachael
authors.initials: R
authors.lastname: Sharman
authors.forename: Karen A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: Ross McD
authors.initials: RM
authors.lastname: Young
authors.forename: James J
authors.initials: JJ
authors.lastname: McGill
mesh_terms: D000293:Adolescent; D044362:Australasia; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D019587:Dietary Supplements / Q000009:adverse effects; D005060:Europe; D056344:Executive Function; D019538:Health Care Surveys; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007361:Intelligence Tests; D009483:Neuropsychological Tests; D009656:North America; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism / Q000523:psychology / Q000628:therapy*; D010818:Practice Patterns, Physicians'; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014443:Tyrosine / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D014443:Tyrosine; D010649:Phenylalanine