Neuropsychological speed tests and blood phenylalanine levels in patients with phenylketonuria: a meta-analysis.
ABSTRACT Although pathogenesis of phenylketonuria is not completely understood, a low phenylalanine diet is effective to prevent severe neurological impairment, mental retardation and behavioural difficulties. Treatment recommendations heavily rely on neuropsychological research; however, single study results are ambiguous, what is reflected in substantial variation of US, British, German, Dutch and French recommendations for blood phenylalanine concentrations for adolescents and adults. We conducted a meta-analysis estimating the influence of age, phenylalanine level, and type of neuropsychological test on effect sizes (standardized differences between controls and patients) of computer-based speed measurements in phenylketonuric patients. The effect of blood phenylalanine level on effect size was more pronounced in children and adolescents than in adults, with choice reaction time being particularly sensitive for phenylalanine concentrations. Results corroborate all recommendations for children. With the exception of the US and Dutch recommendations, all recommendations for adolescents seem to be too liberal. The same effect size is predicted for adult phenylalanine concentrations between 750 and 1500mumol/L not suggesting a preference for any of the published treatment recommendations for adulthood.
Article: Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence.[show abstract] [hide abstract]
ABSTRACT: The National Institute of Health (NIH) published a Consensus Statement on the screening and management of Phenylketonuria (PKU) in 2000. The panel involved in the development of this consensus statement acknowledged the lack of data regarding the potential for more subtle suboptimal outcomes and the need for further research into treatment options. In subsequent years, the approval of new treatment options for PKU and outcome data for patients treated from the newborn period by dietary therapy alone have become available. We hypothesized that a review of the PKU literature since 2000 would provide further evidence related to neurocognitive, psychosocial, and physical outcomes that could serve as a basis for reassessment of the 2000 NIH Consensus Statement. A systematic review of literature residing in PubMed, Scopus and PsychInfo was performed in order to assess the outcome data over the last decade in diet-alone early-treated PKU patients to assess the need for new recommendations and validity of older recommendations in light of new evidence. The majority of publications (140/150) that contained primary outcome data presented at least one suboptimal outcome compared to control groups or standardized norms/reference values in at least one of the following areas: neurocognitive/psychosocial (N=60; 58 reporting suboptimal outcomes); quality of life (N=6; 4 reporting suboptimal outcomes); brain pathology (N=32; 30 reporting suboptimal outcomes); growth/nutrition (N=34; 29 reporting suboptimal outcomes); bone pathology (N=9; 9 reporting suboptimal outcomes); and/or maternal PKU (N=19; 19 reporting suboptimal outcomes). Despite the remarkable success of public health programs that have instituted newborn screening and early introduction of dietary therapy for PKU, there is a growing body of evidence that suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology and maternal PKU outcomes are suboptimal. The time may be right for revisiting the 2000 NIH Consensus Statement in order to address a number of important issues related to PKU management, including treatment advancements for metabolic control in PKU, blood Phe variability, neurocognitive and psychological assessments, routine screening measures for nutritional biomarkers, and bone pathology.Molecular Genetics and Metabolism 101(2-3):99-109. · 3.19 Impact Factor
Article: Serum vitamin B12 concentrations within reference values do not exclude functional vitamin B12 deficiency in PKU patients of various ages.[show abstract] [hide abstract]
ABSTRACT: Homocysteine (Hcy) and in particular methylmalonic acid (MMA) are considered reliable parameters for vitamin B(12) status in healthy individuals. Phenylketonuria (PKU) patients are at risk for functional vitamin B(12) deficiency based on their diet. The aim of this study was to investigate the prevalence of functional vitamin B(12) deficiency in continuously treated PKU patients and the association of parameters of vitamin B(12) and metabolic control. In 75 continuously treated PKU patients of 1-37 years of age, serum vitamin B(12) concentrations, plasma Hcy, MMA, and phenylalanine concentrations were studied. Eight patients had vitamin B(12) concentrations below normal. Out of these eight patients, two had elevated MMA and/or Hcy concentrations. Ten other patients with normal vitamin B(12) concentrations had elevated concentrations of MMA and/or Hcy. A vitamin B(12) concentration within the reference range does not automatically imply a sufficient vitamin B(12) status. We recommend measuring serum MMA, or alternatively plasma Hcy, yearly in all PKU patients to diagnose functional vitamin B(12) deficiency.Molecular Genetics and Metabolism 10/2010; 102(1):13-7. · 3.19 Impact Factor