Neuropsychological effects of subsequent exposure to phenylalanine in adolescents and young adults with eariy‐treated phenylketonuria

Abstract

Severe mental handicap in phenylketonuria (PKU) can be prevented if dietary treatment is implemented at birth. Controversy remains about the optimum age for terminating treatment. A group of adolescents and young adults with PKU from the West of Scotland Register was identified which had received early treatment, been well-controlled on diet, ceased treatment at 10 years old and subsequently were hyperphenylalaninaemic for 3 years or more. They were given a battery of neuropsychological tests and their results were compared with those of on-diet subjects with PKU and normal controls. The findings generally supported the view that dietary cessation at age 10 is sufficient to prevent a substantial reduction of cognitive and motor ability, and that the central nervous system is probably mature enough to withstand the toxic effects of high blood phenylalanine by then. However, there were minor indications, in keeping with Welsh et al.'s hypothesis [M.C. Welsh, B.F. Pennington, S. Ozonoff, B. Rouse & E.R.B. McCabe (1990) Neuropsychology of early-treated phenylketonuria: specific executive function deficits.

Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria

“…Of 15 studies reporting executive function assessments for adults with early-treated PKU and age/gender matched controls without PKU, 13 studies reported mean test scores with variance estimates and were subsequently included in the MA (Antenor-Dorsey et al, 2013;Burgard et al, 1997;Channon et al, 2007;Feldmann, Denecke, Grenzebach, & Weglage, 2005;Griffiths, Paterson, & Harvie, 1995;Luciana, Sullivan, & Nelson, 2001;Moyle, Fox, Bynevelt, Arthur, & Burnett, 2006Pietz et al, 1998Pietz et al, , 1995Ris et al, 1997;Sundermann et al, 2011;Ullrich et al, 1996). The MA effect sizes using Hedges g found significant differences between adults with early-treated PKU and unaffected controls of 0.74 for attention (11 study arms; 252 participants, p < 0.0001), 0.41 for inhibitory control (6 study arms; 119 participants, p = 0.047), and 0.43 for cognitive flexibility (7 study arms; 157 participants, p = 0.006).…”

Biopterin responsive phenylalanine hydroxylase deficiency

“…It has been difficult to comply with this treatment. [7][8][9][10][11][12][13][14][15][16][17] In order to maintain optimal mental functioning in patients with PKU, a search for better methods of treatment has been on going. These methods include enzyme therapy, competition with transport of Phe to the brain, and potentially gene therapy.…”

Neuropsychological Functioning in Early-Treated Phenylketonuria – A Review

“…In total, 50% of their PKU sample scored 1 SD below the normative mean on at least one of the tasks, whereas only 4.7% of the control sample presented with altered functioning. Griffiths et al [48] also showed that off-diet adolescents performed significantly worse than age-matched controls on the Purdue pegboard task. Poorer fine motor performance is thought to be related to higher PHE levels [8,19] .…”