Phenylketonuria in adulthood: A collaborative study
ABSTRACT During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.
- SourceAvailable from: Annet M Bosch[Show abstract] [Hide abstract]
ABSTRACT: Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive disorder of phenylalanine metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH; EC 22.214.171.124). Cognitive problems, neuropsychological abnormalities and psychosocial problems have been reported frequently in children and adolescents with PKU, even in those who are treated early and continuously. However, the developmental consequences in adulthood of growing up with PKU are not well known. The aim of this study was to assess the course of life, sociodemographic outcomes and health-related quality of life in young adult patients with PKU identified on neonatal screening who were continuously on treatment. A total of 32 PKU patients 18 to 30 years old completed the Course of Life questionnaire, the RAND-36 Health Survey, and the cognitive scale of the TNO-AZL Adult Quality of Life (TAAQoL) questionnaire. The results of the Course of Life and Health-Related Quality of Life questionnaires were comparable to controls, except that a higher percentage received special education in primary school. Their educational attainment, however, was comparable to that of their peers. The results of this study demonstrate that although PKU is a chronic disease with the burden of strict dietary control, early and continuously treated patients with PKU can have a normal health-related quality of life and course of life.Journal of Inherited Metabolic Disease 03/2007; 30(1):29-34. DOI:10.1007/s10545-006-0433-6 · 4.14 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: It remains a question why some patients with phenylketonuria (PKU) have high IQ and low brain phenylalanine (Phe) concentrations in spite of high blood Phe levels. One possible explanation for the low brain Phe concentrations in these patients would be a reduced transport of Phe across the blood-brain barrier. The 4F2hc/LAT1 complex has been suggested to be the most important molecular component responsible for this transport. To test the hypothesis that structural variant(s) in the genes encoding 4F2hc and LAT1 might result in a complex with reduced affinity for Phe, we have screened the two genes for sequence variants in a group of 13 PKU patients with a low ratio of brain to blood Phe concentrations. Several common sequence variants were identified, but none of these is predicted to affect the resulting protein product. Our data suggest that individual vulnerability to Phe in patients with PKU is not due to structural variants in the 4F2hc/LAT1 complex.Molecular Genetics and Metabolism 01/2006; 86 Suppl 1:S119-23. DOI:10.1016/j.ymgme.2005.07.031 · 2.83 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Newborn screening programs in the United States are evolving in concert with technologic advances in analytic chemistry and medicine. Many more disorders are being identified on dried filter paper blood spots without fundamentally altering the basic principles first put forward in the 1960s. Some disorders have been added without researchers knowing if there is a true benefit to early diagnosis and treatment; some disorders currently being detected will merit little or no follow-up in the future. The general principles underlying newborn screening are discussed, as are the individual disorders screened in most programs. The expanding and evolving impact of tandem mass spectrometry on newborn screening is also explored.Pediatric Clinics of North America 07/2004; 51(3):803-18, xii. DOI:10.1016/j.pcl.2004.01.009 · 2.20 Impact Factor