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.
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REFERENCES
Azen C, Koch R, Friedman E, et al (1991) Intellectual development in 12 year old children treated for phenylketonuria. Am J Dis Child 145: 35–39.
Berry HK, Bofinger MK, Hunt MM, Phelps PJ, Guilfoyle MB (1982) Reduction of cerebrospinal fluid phenylalanine after oral administration of valine, isoleucine and leucine. Pediatr Res 16: 751–755.
Bickel H, Gerrard J, Hickmans EM (1953) Influence of phenylalanine intake on phenylketonuria. Lancet 2: 812–813.
Dyer CA (2000) Comments on the neuropathology of phenylketonuria. Eur J Pediatr 2: S107–108.
Guldberg P, Gutter F (1994) Broad-range DGGE for single-step mutation scanning of entire genes: application to human phenylalanine hydroxylase gene. Nucleic Acids Res 22: 880–881.
Guldberg P, Rey F, Zschocke J, et al (1998) A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am J Hum Genet 63: 71–79.
Guthrie R (1961) Blood screening for phenylketonuria. J Am Med Assoc 178: 863.
Kayaalp E, Treacy E. Waters PJ, et al (1997) Human PAH mutation and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations. Am J Hum Genet 61: 1309–1317.
Koch R, Moats R, Guttler F, Guldberg P, Nelson M (2000) Blood-brain phenylalanine relationships in persons with phenylketonuria. Pediatrics 106: 1093–1096.
Kure S, Hou DC, Ohura T, et al (1999) Tetrahydrobiopterin responsive phenylalanine hydroxylase deficiency. J. Pediatr 135: 375–378.
Lou H (1985) Large doses of tryptophan and tyrosine as potential therapeutic alternative to dietary phenylalanine restriction in phenylketonuria. Lancet 2: 150–151.
Pietz J, Kreis R, Rupp A, et al (1999) Large neutral amino acids block phenylalanine transport into brain tissue in phenylketonuria. J Clin Invest 103: 1169–1178.
SAS Institute Inc. (1989) SAS/STAT User's Guide, Version 6, 4th edn, volumes 1 and 2. Cary, NC: SAS Institute Inc.
US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Child Health and Human Development (2001) Report of the NIH Consensus Development Conference on Phenylketonuria (PKU): Screening and Management.
Williamson ML, Dobson JC, Koch R (1977) Collaborative study of children treated for phenylketonuria: study design. Pediatrics 60: 815–821.
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Koch, R., Burton, B., Hoganson, G. et al. Phenylketonuria in adulthood: A collaborative study. J Inherit Metab Dis 25, 333–346 (2002). https://doi.org/10.1023/A:1020158631102
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DOI: https://doi.org/10.1023/A:1020158631102