Date of Award

Spring 4-6-2021

Author's School

Graduate School of Arts and Sciences

Author's Department


Degree Name

Master of Arts (AM/MA)

Degree Type



Phenylketonuria (PKU) is an autosomal recessive disorder characterized by mutations in phenylalanine hydroxylase genes. As a result, phenylalanine (Phe) metabolism is disrupted, and this amino acid accumulates in blood and tissue (Pietz, 1998; Scriver et al., 2000). Although the most severe symptoms of PKU may be avoided by early detection and treatment, many individuals with early-treated PKU still experience difficulties in executive function, attention, and processing speed (Antenor-Dorsey et al., 2013; Araujo et al., 2013; Christ et al., 2020; Hawks, Strube, Johnson, Grange, & White, 2018; Hood, Grange, Christ, Steiner, & White, 2014; Janos et al., 2012; White et al., 2002). Of particular relevance to the current investigation are the executive abilities of strategic processing, working memory, and inhibition. The present study is the first to investigate the rate of blood Phe level increase as a function of increasing age and its relationship to these executive abilities, with the hypothesis that a greater rate of change is associated with poorer executive performance. Repeated blood Phe measures were collected from children ages 0-24 years of age with early- and continuously-treated PKU whose executive abilities were assessed (n = 73, males = 37, females = 36, mean age at assessment = 14.3 years). The relationships between blood Phe and semantic clustering scores (strategic processing), recognition span scores, n-back errors (working memory), and go-no-go commission errors (inhibition), as well as their interactions with age, were examined using hierarchical linear modeling to account for longitudinal dependencies. Consistent with hypotheses, better semantic clustering and recognition span scores were associated with less increase in blood Phe as age increased, whereas more n-back and go-no-go errors were associated with greater increase in blood Phe as age increased. Continued efforts to specify the time frame during which rates of blood Phe increase and executive performance are most strongly related will aid in identifying developmental periods during which PKU treatment adherence may be especially important for mitigating executive deficits.


English (en)

Chair and Committee

Desiree White

Committee Members

Lori Markson, Michael Strube