Waisbren SE, Brown MJ, de Sonneville LMJ, Levy HL. Review of neuropsychological functioning in treated phenylketonuria: an information processing approach. Acta Prediatr 1994;(Suppl407):98-103. Stockholm. ISSN 0803-5326 Phenylketonuria is no longer associated with mental retardation and other devastating neurological effects. Nonetheless, learning disabilities and IQ loss are common, even in early-treated individuals. Until recently, IQ was used as the sole measure of mental functioning in this population. As specific academic deficits were recognized and as a greater variety of tests became available, evaluation of children with phenylketonuria has included neuropsychological testing. A review of the 21 published reports highlights the areas of consensus and the need for additional well designed studies in the future. Problem solving, particularly abstract reasoning and executive functions, appears to be impaired in children with phenylketonuria. Reaction time, or speed of mental processing, appears to be the other important area affected in PKU. An information processing model is presented as a paradigm for further research and development of remedial strategies for children with phenylketonuria.

Follow‐up of early‐treated children with PKU has shown that diet discontinuation in childhood presents risks of cognitive and emotional dysfunction in a substantial number of adolescents and young adults. This dysfunction includes IQ loss, mental processing abnormalities, learning difficulties, anxiety and personality disorders. In addition, neurologic deterioration has been reported in several such individuals. As consequence of this current understanding of PKU, diet continuation, at least through adolescence and in the young adult years, is now recommended. Many centers are extending this to policy of “diet for life”. This represents major challenge to adolescents and their families. Metabolic control using the criteria applied during childhood is virtually impossible to achieve past 12 years of age. Time constraints, social pressures, financial limitations and growing independence from the family combine to interfere with dietary control. Added to these difficulties are the biological changes during teenage years which reduce phenylalanine tolerance. To meet these challenges, we have identified number of psychosocial factors that interfere with adherence to medical recommendations. The factors most highly related to metabolic control were social support for the diet and positive perceptions of treatment. This information has led to the development of support programs for adolescents and young adults with PKU. These programs include an annual New England maternal PKU camp, resource mothers program in which mothers of young children with PKU are matched to women with PKU who are either planning pregnancy or are pregnant and assist with meal planning, cooking, metabolic monitoring, and transportation to medical appointments as well as provide enormous emotional support to these young women, and PKU CORPS which brings together on‐diet adolescents for training and emotional support and then matches them with younger phenylketonuric children on diet. The benefits of these programs are becoming clear in terms of improved metabolic control, successful re‐institution of diet, a more comfortable acceptance of PKU and better self‐image.

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child‐bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine‐restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.