Behaviour and school achievement in patients with early and continuously treated phenylketonuria

Abstract

Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a group, demonstrated more problems in task-oriented behaviour and average academic performance than did matched controls. Interestingly, whereas male PKU patients were rated significantly lower on introversion by their teachers, female patients were rated significantly higher on introversion and lower on extraversion than matched controls. This sex difference was also reflected in the relationship between measures of dietary control and the behaviour clusters, suggesting that male and female patients respond differently to elevated Phe levels or the stress associated with PKU. The teacher rating on average academic performance of the PKU patients was associated with recent level of dietary control, which suggests that it might be improved by more strict adherence to the diet. In addition, academic performance correlated negatively with the behaviour cluster negative task orientation. Further studies are recommended to obtain a more complete evaluation of this relationship and to replicate the current findings on larger samples. Over the years a number of studies have examined behaviour and school achievement in patients with early treated phenylketonuria (PKU; McKusick 261600). In general, these studies have found that despite early treatment with a phenylalanine (Phe)-restricted diet, PKU patients demonstrate more behavioural and school problems than do healthy controls. The behaviour problems include both internalizing symptoms (e.g. solitary, unresponsive, anxious, depressed mood: Pietz et al 1997; Smith et al 1988; Weglage et al 1992) and externalizing symptoms (e.g. hyperactive, talkative, impulsive, restless: Hendrikx et al 1994; Kalverboer et al 1994; Realmuto et al 1986; Smith et al 1988), but not antisocial or socially negative symptoms (e.g. lying, teasing, disobedience: Kalverboer et al 1994; Pietz et al 1997; Smith et al 1988). With respect to school achievement, studies have shown that patients with early treated PKU more often repeat classes or need special tutoring (Berry et al 1979; Brunner et al 1983; Koch et al 1987; Rey et al 1996; Verkerk 1995), have to work harder than healthy controls to achieve the same results (Weglage et al 1993), or have specific deficits in arithmetic achievement scores (Azen et al 1991; Berry et al 1979; Fishler et al 1987; Koch et al 1987; Weglage et al 1993). Nevertheless, many questions regarding the behavioural and school problems of patients with early treated PKU remain unanswered. For instance, the relationship between behavioural and school problems on the one hand and levels of dietary control on the other is still relatively unclear. The few studies that examined this relationship, have focused primarily on children in primary school (Azen et al ...

Differential effects of low-phenylalanine protein sources on brain neurotransmitters and behavior in C57Bl/6-Pahenu2 mice

“…Female PKU mice showed more severe responses to the high-phe casein diet reflected in reduced vertical activity in the open field test compared to male PKU mice, as well as negative effects on body growth, and renal and liver mass [36]. These sex differences persist into human PKU as female behaviors were rated differently by their teachers compared to males with PKU [58]. Taken together, the evidence suggests that males and females respond differently to elevated phe levels or the stress that accompanies having PKU [58].…”

Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU

“…The target range of blood Phe concentrations was 200-500 mmol/L for all ages according to Dutch recommendations at that time (Stemerdink et al 2000). The means of Phe concentrations of blood samples collected at the seven time points were subsequently used to decide on metabolic control and to include or exclude data on tolerance of the individual patient at that point.…”

Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism

“…PKU is the prototypical human Mendelian disease (OMIM 261600; overall incidence of 1 in 10,000) resulting from impaired activity of phenylalanine hydroxylase (PAH), the enzyme necessary to convert phenylalanine (PHE) to tyrosine. This deficiency causes hyperphenylalaninemia (HPA), which is especially harmful for the brain during the first years of life, resulting in variable neurological and mental impairments [2,3,4]. Previous evidence from our group demonstrated that the accumulation of PHE in the brain of BTBR-Pah enu2 (ENU2) mice impairs protein levels and enzymatic activity of the tryptophan hydroxylase, the rate-limiting enzyme responsible for serotonin biosynthesis [5], and that the serotonin reduction in the brain causes cortical morphological alterations such as a reduction in the dendritic spine density and maturation [6].…”