Executive function in treated phenylketonuria as measured by the one‐back and two‐back versions of the continuous performance test

Abstract

The executive dysfunction hypothesis in treated phenylketonuria was investigated by means of the one-back and two-back versions of the continuous performance test. Eleven non-retarded, primary school-age children with classical phenylketonuria who had been treated early and continuously were indistinguishable from healthy, matched controls on the measures and test performance was not predicted by historical or concurrent plasma phenylalanine concentrations. Mean lifetime phenylalanine concentrations for the phenylketonuric subjects were within ranges currently recommended as dietary optima in the United Kingdom. The negative neuropsychological test findings add weight to the rationale for this policy.

Efficacy and safety of sapropterin dihydrochloride in patients with phenylketonuria: A meta‐analysis of randomized controlled trials

“…Therefore, the differences in the change in Phe level from baseline between sapropterin and the control group were greatest at 4 weeks after the initiation of sapropterin treatment and became less pronounced during the 26‐week follow‐up period. Several studies have shown that when blood Phe concentration exceeds 600 μmol L −1 , executive and cognitive function deteriorate. Sapropterin reduced blood Phe concentration to normal range in a short time (within 6 weeks), which might minimize the risk of cognitive impairments.…”

Executive Functioning and Speed of Processing in Phenylketonuria.

“…Another difficulty for the executive hypothesis in adulthood is that if cognitive impairment in PKU is linked to dopaminergic PFC depletion, direct relationships between past or present Phe levels and cognitive performance might be expected. Previous studies have provided mixed evidence in this respect, with some authors reporting positive correlations with attentional and executive performance on some measures (e.g., Smith et al, 1996), others failing to find significant relationships with Phe levels (e.g., Griffiths et al, 1998;Griffiths, Tarrini, & Robinson, 1997), and some finding negative relationships between Phe levels and performance (e.g., Diamond et al, 1997;Welsh et al, 1990). There was little evidence of a relationship with cognitive performance in the present study, as all correlations with Phe levels except one were nonsignificant.…”

“…Several studies have described dysfunction on some executive tasks in children and adolescents with PKU, even with continuous dietary treatment (e.g., Diamond, Prevor, Callender, & Druin, 1997;Huijbregts, de Sonneville, van Spronsen, Licht, & Sergeant, 2002;Stemerdink et al, 1999;Welsh, Pennington, Ozonoff, Rouse, & McCabe, 1990;White, Nortz, Mandernach, Huntington, & Steiner, 2002). Other researchers have failed to find deficits in children and adolescents (e.g., Griffiths, Campbell, & Robinson, 1998;Luciana, Sullivan, & Nelson, 2001;Mazzocco et al, 1994;Stemerdink et al, 1995). Methodological issues including small sample sizes and cognitive measures of differing sensitivity make it difficult to draw firm conclusions.…”

Executive functioning in children and adolescents with phenylketonuria

“…Immediate treatment (dietary restriction of phe) is indicated on diagnosis (usually by newborn screening). Early and consistent treatment leads to intelligence quotients (IQs) in the normal range (2, 3). However, cognitive or neuropsychological deficits may be present even in optimally managed patients (4–16).…”