Parenting Styles and Coping Strategies in PKU Early Detected Children

Abstract Phenylketonuria (PKU) requires tight control to prevent neurocognitive impairment but reports show that patients may present mild cognitive defects related to higher impulsivity. We hypothesize that chronic intervention may influence the parents and child bonding and the child´s resources to face problems. To describe the PKU parenting styles perceived by the children (PS) and their coping strategies (CS) assessing their relationship with impulsivity, 30 early diagnosed and adequately treated PKU children and 30 non PKU aged-paired controls (CG) were compared. The Argentine Children´s Coping Questionnaire, Argentine Scale Perception of the Relationship with Parents, WISC IV Comprehension Subtest, and CPT II test were administered. PKU PS were based on control: strict to pathologic in the mother and acceptable in the father (both p<0.05 vs. CG). Children significantly sought greater support and showed less emotional control when facing conflicts. These characteristics positively correlated with maternal control r:.383 and r:.398 (both p<0.05). Impulsivity was higher in PKU (p<0.05) but didn´t associate with PS or CS. Maternal strict control wasn´t linked to the higher impulsivity found (possibly neurobiologically based). Nevertheless, if both factors are present, patients may develop a psychological and/or behavioral trait of greater dependency and impulsivity that must be considered in their follow-up.

Bone Health in Adults with Phenylketonuria: A Cross-Sectional Study

Abstract Available literature documenting BMD in patients with PKU is mostly reported among heterogeneous populations including adults and children. We aim to describe the bone health status among adults (aged >18 years) affected with Phenylketonuria (PKU) and to evaluate the effect of diet and exercise on bone mineral density (BMD). Sample size of the study population was 27. Enrolled patients underwent multi-site Dual-energy X-ray absorptiometry (DXA) scan and laboratory tests. Nutritional and physical activity records were obtained on each subject to ascertain bone health. BMD in patients with PKU was low normal. 14% of the study subjects were found to have osteoporosis in at least one measured skeletal site. 70% had low BMD in one or more of the measured skeletal sites. BMD score was lowest at radius. Moderate correlation was observed between femoral and radial BMD and serum calcium level. Dietary intake of vitamin A was moderately correlated with BMD T-scores in femur. Our results indicate that BMD in patients with PKU is low normal with better BMD with vitamin A intake, trend towards better bone health with physical exercise and Sapropterin intake.

Linguistic Validation of the Phenylketonuria - Quality of Life (PKU-QOL) Questionnaire Into Brazilian Portuguese

Abstract The phenylketonuria - quality of life (PKU-QOL) questionnaire was developed to assess the impact of phenylketonuria (PKU) and its treatment on the health-related quality of life (HRQL) of patients and their caregivers. Available in four versions (child, adolescent, adult and parent), it was developed and validated in eight countries. The objective of this study was to linguistically validate the PKU-QOL questionnaire in Brazilian Portuguese for use in Brazil by clinicians who take care of PKU patients. The translation method used a standard linguistic validation process. The British English version served as a basis for translation. No major cultural or semantic issues were found during the process. The main difficulty was the use of the acronym "PKU" in the first translations. During the cognitive interviews, respondents made the confusion between the disease itself and the food supplement since it is written "PKU" or "COMIDA-PKU" on the packaging of the product. To overcome this issue, it was decided to use fenilcetonuria (fenil) or fenil alone throughout all versions. The PKU-QOL will be valuable for Brazilian healthcare providers in individualizing treatment and managing patients with PKU.

Phenylalanine Hydroxylase (PAH) Genotyping in PKU Argentine Patients

Abstract Phenylketonuria (PKU, OMIM 261600) is predominantly caused by mutations in the PAH gene. One hundred and three Argentine PKU patients were studied by Sanger sequencing; 101 were completely characterized (90.3% were compound heterozygotes). Fifty-four different pathogenic variants were identified. Mutations were distributed all along the PAH gene but concentrated in exon 7 (26%), 12 (12%), 11 (10%), and 6 (10%). 77% were missense, and 77% affected the enzyme catalytic domain, nine mutations accounted for 57% of 179 studied alleles: p.Arg261Gln (Allele frequency(AF):10.6%), c.1066-11G>A (AF:9,5%), p.Arg408Trp (AF:8,3%), p.Tyr414Cys (AF:5,5%), p.Ala403Val, p.Val388Met, and p.Arg158Gln (AF: 5% each), p.Leu48Ser, and p.Ile65Thr (AF:4% each). The predicted phenotype was assigned by Guldberg´s arbitrary value (AV) and compared with the clinical phenotype based in tolerance to Phe intake. 29.1% (n:30) were hyperphenylalaninemias, 18.5% (n:19) mild-PKU, 27.2% (n:28) moderate-PKU and 25.2 % (n:26) classical-PKU. Genotype/phenotype correlation was statistically significant (p<0.001) Overall concordance was 62,5%: 93.3% in hyperphenylalaninemia, 64.7% in mild-PKU and 65.4% in classical patients. The moderate-PKU showed a weak concordance (17%) with milder AV prediction than clinical assessment. 74% of discordant moderate patients harbored p.Arg261Gln, and p.Val388Met. Our cohort is highly heterogeneous, with predominant Mediterranean influence (mainly Spanish), but with differences with other Latin-American countries.

Detección temprana de Hipotiroidismo congénito y Fenilcetonuria a través del cribado neonatal en el estado Cojedes / Early detection of Phenylketonuria and congenital Hypothyroidism with newborn screening

El hipotiroidismo congénito y la fenilcetonuria son trastornos del metabolismo cuyas consecuencias clínicas ocasionan un grave retardo mental, así como la aparición de secuelas físicas y neurológicas que afectan el desarrollo del niño. Una de las herramientas que fortalecen el diagnostico precoz es el cribado neonatal. La finalidad de esta investigación es determinar en forma temprana la incidencia casos de hipotiroidismo congénito y fenilcetonuria (PKU) neonatal en el estado Cojedes durante el período Enero de 2008 - Diciembre de 2014. Métodos: La investigación se enmarcó en un diseño de investigación no experimental, retrospectivo y descriptivo, dirigida a una población conformada por recién nacidos vivos a quienes se les realizó en sangre seca sobre papel de filtro la cuantificación de la hormona estimulante de tiroides (TSH) por método ELISA y prueba fluorescente para la cuantificación de la concentración de fenilalanina (PHE). La técnica de recolección de datos empleada fue la Escala de Estimación. Resultados: De 54.152 recién nacidos vivos en este periodo se realizó el cribado metabólico a 35.988 recién nacidos lo que representa un 66,46 % de la población sometida al mismo. Se registraron 4 casos positivos para TSH constituyendo un 0,01 %, representando el 50 % el sexo masculino y 50 % el sexo femenino, con una incidencia de 1:2276 y ningún caso para PKU. Recomendación: Ofrecer información de la importancia de la Pesquisa o Cribado Metabólico Neonatal de estas patologías a las mujeres embarazadas.

Congenital hypothyroidism and phenylketonuria are metabolic disorders which may have clinical consequences and cause severe mental retardation, and the appearance of physical and neurological sequelae that affect child development. One of the tools that strengthen early diagnosis is neonatal screening, The purpose of this research is to determine the incidence early cases of congenital hypothyroidism and phenylketonuria ( PKU) neonatal in Cojedes state during the period January 2008 - December 2014. The research was part of a pattern of non-experimental, retrospective and descriptive research, led to a population consisting of live births who were held in dried blood on filter paper quantitation of thyroid stimulating hormone (TSH) ELISA method and fluorescent probe for quantification of the concentration of phenylalanine (PHE). The data collection technique used was the rating scale. Results: Of 54,152 live births in this period metabolic screening was performed at 35,988 newborns which represent 66.46 % of the population subjected to it. 4 positive cases were recorded for TSH constituting 0.01 %, representing 50% males and 50 % females, with an incidence of 1: 2276 and no case for PKU. Recommendation: Provide information on the importance of Neonatal Metabolic Research or screening of these diseases to pregnant women.

Technological Journey From Colorimetric to Tandem Mass Spectrometric Measurements in the Diagnostic Investigation for Phenylketonuria

Abstract Phenylalanine analysis for phenylketonuria (PKU) detection in newborn screening (NBS) was chosen as the model system to describe how advancements in laboratory technology improved laboratory performance. These advancements have made NBS programs better and have improved the health outcomes of the affected newborn through improvements in accurate early detection over the past 50 years. The most current state-of-the-art technology, tandem mass spectrometry (MS/MS), has proven that it is now the choice in almost all modern NBS facilities because it is a versatile instrument that continues to grow in its application not just for amino acid and acylcarnitine detection but for other metabolites and disorders such as lysosomal storage diseases and second-tier detection of some screen-positive results. The use of MS/MS will continue to expand, even with the anticipated introduction and expansion of molecular screening methods into NBS programs. Regarding technological advancements, the future of NBS will include even newer technologies and approaches that will enhance the detection and treatment of newborns affected by PKU and other inborn errors of metabolism.

Fenilquetonuria e ingesta de selenio, zinc y vitamina E / Phenylketonuria and intake of selenium, zinc and vitamine E

La Fenilquetonuria (PKU) se produces por la deficiencia de la enzima Fenilalanina Hidroxilasa, causando un aumento plasmático de fenilalanina (FA). El objetivo del presente estudio fue evaluar la ingesta de Selenio (Se), Zinc (Zn) y vitamina E en niños PKU menores de 13 años de edad, que estaban en dieta restringida en FA y recibiendo fórmula especial sin FA. Método: Se incluyeron 50 PKU entre los 0 y 13 años y en control en el INTA, Universidad de Chile. Se analizó ingesta de vitamina E, Se y Zn, se midió nivel de FA en plasma y se evaluó estado nutritional. Resultados: Las recomendaciones diarias de Se y Zn se cubren en un 100 por ciento con la dieta habitual de PKU. Pero al excluir la formula sin FA, la cobertura de ambos nutriente disminuye a 45 por ciento y 20 por ciento respectivamente. La ingesta de vitamina E se cubre en forma natural por el consumo de aceites vegetales y al incluir la vitamina de la fórmula sin FA, la cobertura se incrementaba 5 veces sobre su recomendación. El nivel de FA en la sangre fue en promedio de 5.4 mg/dL, considerado un buen control metabólico. El 64 por ciento tenía un estado nutritional normal, el 30 por ciento estaba sobrepeso u obeso y un 6 por ciento riesgo de desnutrición. Conclusiones: Se concluye que la dieta de niños PKU cubre las recomendaciones de los micronutrientes: Zn, Se y vitamina E. No obstante se debe enfatizar la importancia que tiene la fórmula sin FA para cumplir con las recomendaciones nutricionales, especialmente de micronutrientes.

Phenylketonuria (PKU) is caused by a deficiency of the enzyme Phenylalanine Hydroxylase, resulting in increased plasma Phenylalanine (Phe). The aim of this study was to assess the intake of Selenium (Se), Zinc (Zn) and vitamin E in PKU children, who were on a diet restricted in Phenylalanine (Phe) and receiving a special formula without Phe. Method: the study included 50 PKU children between 0 and 13 years controled at INTA, University of Chile. We analyzed intake of vitamin E, Se and Zn, measured Phe plasma levels and assessed nutritional status. Results: The daily recommendations of Se and Zn were 100 percent covered with the usual PKU diet. By excluding the formula without Phe, the coverage of both nutrients decreased to 45 percent and 20 percent respectively. The intake of vitamin E was covered by the consumption of vegetable oils and when the formula without Phe was included, the coverage was increased 5 times over the recommended levels. Blood Phe level remained on average at 5.4 mgldL, considered a good metabolic control. Conclusions: We conclude that the diet of PKU children covered the recommended levels of Zn, Se and vitamin E. However, it should be emphasized the importance of the formula without Phe to meet nutritional recommendations, particularly of micronutrients.

The Study of DNA Mutations of Phenylketonuria in Koreans

PURPOSE: Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations. METHODS: DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA). RESULTS: We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of BH4 responsive patients were analyzed and were divided into two groups: BH4 medication-only group and BH4 medication with diet therapy group. In the BH4 medication-only group and BH4 medication with diet therapy group, R241C was the most common mutation. CONCLUSION: Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.

Superiority for Neonatal Phenyiketenuria Screening by Chemical Fluorometric Enzyme Immunoassay / 医学研究杂志

0.05).Among 67 040 neonates screened by CFELA,11 1/6 096 were found to be defective;194 012 neonates screened by BIA,21 1/9 239 were found to be defective.Conclusion The guantitative CFELA is more sensitive and rapid,and should be a worthy method being recommend for major screening.

Design of Phenylketonuria Fluorescence Detection Optical System / 医疗卫生装备

Objective To design a new type of fluorescence detection optical system for dedicated neonatal PKU screening. Methods The system selects super-luminance UVLED for excitation light source, uses different diameter quartz fiber and Y -type optical fiber which consists of glass fiber bundles, and self focusing optical fiber for collimating light and photomultiplier tubes for testing. Results The system has many features, such as simple structure, small size and high sensitivity. Conclusion The clinic screening requirements are met by the system and a new means of rapid detection is provided for PKU screening in large quantities.