Phenylketonuria in adulthood: a collaborative study (original) (raw)
Adults with untreated phenylketonuria: out of sight, out of mind
The British Journal of Psychiatry, 2008
Phenylketonuria is a recessively inherited metabolic disorder which, unless it is treated early enough with a phenylalaninerestricted diet, leads to severe intellectual disabilities. The overall prevalence of phenylketonuria in the UK is about 1 per 10 000 2 and published guidelines suggest that treatment needs to be early and lifelong. Neonatal newborn screening for phenylketonuria began in the late 1960s and those treated early had a very good outcome. 1 However, those born before neonatal screening began were not normally treated, as they already had severe intellectual disabilities, assumed to be irreversible. Our study aimed to trace all those with untreated phenylketonuria and severe intellectual disabilities in the UK and to examine their range of difficulties, as a prelude to a randomised controlled trial of phenylalanine-restricted diet in people with previously untreated phenylketonuria.
Long-term pharmacological management of phenylketonuria, including patients below the age of 4 years
JIMD reports, 2012
BH4 therapy is an advancement in the treatment of phenylketonuria, reducing blood phenylalanine (phe) levels and increasing tolerance to natural proteins of responding patients. We report the results of 16 patients undergoing long-term BH4 treatment. Responding patients to BH4 was usually based on 24-h loading tests; a ≥30% decrease in blood phe was considered a positive response. Weekly loading made it possible to identify an additional "slow responder." The 16 responders constitute 24.6% of patients who completed the trial (87.5% of responders in mild hyperphenylalaninemia, 38.1% in mild PKU, and 2.8% in classical PKU).Mean dose of BH4 used was 9.75 ± 0.9 mg/kg per day, during a mean of 62 months. Age at treatment start was below 4 years in seven patients; five of which begun treatment during their first month since birth. All but one patient showed good treatment compliance; six continue on BH4 monotherapy without dietary phe restriction; six showed an increase in phe t...
Phenylketonuria: questioning the gospel
Expert Review of Endocrinology & Metabolism, 2007
Phenylketonuria (PKU) was first described over 70 years ago, treatment was developed 50 years ago and universal newborn PKU screening was introduced 40 years ago. Phenylalanine-restricted dietary treatment has prevented mental retardation in thousands of individuals worldwide. We acknowledge, however, that there is still much to learn in the field. The incidence of mental retardation in untreated PKU is likely to be considerably less than the original estimates. Since dietary control is suboptimal in late childhood, adolescence and adulthood, alternative methods of treatment are being explored. These include large neutral amino acids, phenylalanine ammonia lyase, tetrahydrobiopterin and gene replacement. Evidence has surfaced that the semisynthetic, low-protein diet used to treat PKU may be deficient in certain important nutrients. Maternal PKU treatment may be successful even if initiated as late as 8-10 weeks into pregnancy. A plea is made for the immediate establishment of adult treatment centers for PKU (and other inherited metabolic diseases) for long-term treatment, follow-up and research.
International Journal for Innovation Education and Research, 2019
Phenylketonuria is an inborn error of autosomal recessive genetic metabolism, with partial or total deficiency of the hepatic enzyme phenylalanine hydroxylase, which converts L-phenylalanine into tyrosine, causing accumulation of phenylalanine at brain and serum levels, interfering with brain protein synthesis causing several damages. This study aimed to characterize patients diagnosed with phenylketonuria at the Neonatal Screening Reference Service from 2008 to 2017. Cross-sectional analytical study with a quantitative approach with retrospective data collection from medical records and databases. Data were grouped as baby gender, date of birth, time of birth and neonatal screening examination collection, type of delivery, gestational age and prenatal status, place of origin, phenylketonuria classification and coverage rate of neonatal screening. The sample consisted of 14 patients, where 64% were male, all mothers had prenatal care and the percentage of cesarean delivery prevailed with 57.2%. Of these 85.7% reside in other states of the country and on the classification of the type of phenylketonuria 64.3% have mild phenylketonuria, as for the coverage rate there was a drop in the number of collections in the reference service. This research contributed to characterize the patient diagnosed with phenylketonuria, which allows greater knowledge about the disease carriers, as well as favoring the reduction of irreversible sequels, expenses and morbidity.
Neonatal screening and long-term follow-up of phenylketonuria: the French database
Early Human Development, 2001
Background: In France, neonatal screening of phenylketonuria (PKU) started in 1966. A national association was created in 1978 in order to organise the neonatal screening program and to control the efficacy of the screening and patients' follow-up. Aims: To evaluate the results of the French PKU screening program in terms of hyperphenylalaninaemia epidemiology, efficacy of the screening procedure, management and outcome of the patients. Study design: The national database has been filled-up first with the answers to questionnaires that were sent each year by the PKU patients' physicians, and second with the results of an additional inquiry, which was set up in 1994 in order to investigate diagnosis, treatment, and school outcome of all French PKU patients. Results: PKU was diagnosed in 81.6% of patients with hyperphenylalaninaemia (HPA), non-PKU HPA in 17.2% and cofactor deficiency in 1.1%. From 1980, incidence of PKU has been stable: 1 per 17,124 live births. Sensitivity of the screening procedure was 99.3%. Age at diet initiation regularly decreased to reach 14 days as a median in 1996. Until 1990, median age at diet discontinuation was 6 years of age. Later, strict diet was continued longer (at least, up to 8 -10 years). PKU patients who 0378-3782/01/$ -see front matter D 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 7 8 -3 7 8 2 ( 0 1 ) 0 0 2 2 3 -7 $ On behalf of the Association Francaise pour le Dépistage et la Prévention des Handicaps de l'Enfant (AFDPHE). (L. de Parscau). www.elsevier.com/locate/earlhumdev * Early Human Development 65 (2001) 149 -158
Phenylketonuria in Children and Mothers
Current Directions in Psychological Science, 2009
Phenylketonuria (PKU) is an inborn metabolic error in which metabolism of phenylalanine into tyrosine is disrupted. If the diet of an infant with PKU is not restricted, blood phenylalanine levels are elevated, leading to irremediable brain damage and severe mental retardation. Children with PKU who are placed early and continuously on a low-phenylalanine diet develop normal levels of intelligence, and brain damage is largely prevented. However, if the diet of a mother with PKU is unrestricted during her pregnancy, high phenylalanine levels in her blood can cross the placental barrier and damage the developing fetus in multiple ways. These results demonstrate how genes and environmental factors combine to create prenatal environments that can have profound effects on the growth and development of offspring during infancy and childhood.
Nutritional evaluation of children with phenylketonuria
Sao Paulo Medical Journal, 1999
Context: Dietary phenylalanine (PA) restriction is the most effective form for reducing its excess in the blood and is the only efficient method for treating phenylketonuria. The diet is complex and should be adapted to combine the patients' eating habits, growth and development. It depends basically on the use of industrialized products as substitutes free of PA for proteins that are not fully supplied. Objective: To evaluate the nutritional status of children with phenylketonuria (PKU) by anthropometric measurements and food intake. Design: Cross-sectional study. Setting: Children with PKU attending the Association of Parents and Friends of Handicapped Children (Associação de Pais e Amigos dos Excepcionais -APAE) and normal children attending at municipal day care centers in São Paulo. Participants: 42 children with PKU and 31 normal children aged 1 to 12 of both sexes were assessed in two groups, under and over 7 years of age. Main Measurements: Weight and height measurements. Results: Children with PKU ingested calories, calcium, iron, zinc, and copper below the recommended values, whereas the protein intake was within the normal range. Food intake in the group of normal children was within normality rates. The height/weight Z-score means for children with PKU were 0.47 for those under 7 years and 1.86 for 7 year-olds and over; in normal children the means were 0.97 <7 years and 1.54 ≥7 years, with no statistically significant difference. The height/ age Z-score means were significantly lower in the PKU children <7 years (-1.23) than in the normal controls (0.91).
Follow up of phenylketonuria patients
Molecular Genetics and Metabolism, 2011
In recent years our understanding of the follow up policies for PKU has increased substantially. In particular, we now understand the importance of maintaining control of blood phenylalanine (phe) concentrations lifelong to achieve the best long-term neuropsychological outcomes. The concordance with the follow up strategy remains a key challenge for the future, especially with respect to adolescents and young adults. The recent therapies could ease the burden of the dietary phe restriction for PKU patients and their families. The time may be right for revisiting the guidelines for follow up of PKU in order to address a number of important issues related to PKU management: promotion of breastfeeding to complementary feeding up to 2 years of age for prevention of early growth retardation and later overweight development, treatment advancements for metabolic control, blood phe and tyr variability, routine screening measures for nutritional biomarkers, neurocognitive and psychological assessments, bone pathology, understanding the challenges of compliance and transitioning into adulthood as an individual with PKU and addressing unmet needs in this population.
Nutrient Intake and Growth of Infants with Phenylketonuria Undergoing Therapy
Journal of Pediatric Gastroenterology & Nutrition, 1998
Background: Because of reports of poor growth, a study was conducted for 6 months in 35 infants with classic phenylketonuria diagnosed during the neonatal period who were fed Phenex-1 Amino Acid Modified Medical Food With Iron (Ross Products Division, Columbus, OH, U.S.A.) as their primary protein source.