7,809 results match your criteria Phenylketonuria


Sapropterin dihydrochloride for phenylketonuria and tetrahydrobiopterin deficiency.

Authors:
Nenad Blau

Expert Rev Endocrinol Metab 2010 Jul;5(4):483-494

a Zürich Center for Integrative Human Physiology (ZIHP), Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.

Sapropterin dihydrochloride is the first registered synthetic form of the naturally occurring cofactor and cosubstrate, tetrahydrobiopterin (BH4). It is essential for the conversion of phenylalanine (Phe) by phenylalanine-4-hydroxylase (PAH) to tyrosine. BH4 is also the co-factor of rate-limiting enzymes involved in the synthesis of monoamine neurotransmitters. Read More

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http://dx.doi.org/10.1586/eem.10.39DOI Listing

Admissions and Cost of Hospitalisation of Phenylketonuria: Spanish Claims Database Analysis.

Clin Drug Investig 2019 Feb 18. Epub 2019 Feb 18.

BCN Health Economics and Outcomes Research S.L., Barcelona, Spain.

Background: Phenylketonuria is a well-known rare disease included in the neonatal screening of many countries. Therefore, there are few published data on the admissions and costs of phenylketonuria in Spain.

Objective: The objective of this study was to assess the number of admissions and the economic burden of phenylketonuria in Spain. Read More

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http://dx.doi.org/10.1007/s40261-019-00760-1DOI Listing
February 2019

Glycomacropeptide: long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU.

Orphanet J Rare Dis 2019 Feb 15;14(1):44. Epub 2019 Feb 15.

Dietetic Department, Birmingham Childrens Hospital, Steelhouse Lane, Birmingham, B4 6 NH, UK.

In phenylketonuria, casein glycomacropeptide (CGMP) requires modification with the addition of some essential and semi essential amino acids to ensure suitability as a protein substitute. The optimal amount and ratio of additional amino acids is undefined.

Aim: A longitudinal, parallel, controlled study over 12 months evaluating a CGMP (CGMP-AA2) formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU. Read More

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http://dx.doi.org/10.1186/s13023-019-1011-yDOI Listing
February 2019

Mutation spectrum of PAH gene in phenylketonuria patients in Northwest China: identification of twenty novel variants.

Metab Brain Dis 2019 Feb 12. Epub 2019 Feb 12.

Graduate School of Peking Union Medical College, Beijing, 100730, China.

This study was performed to analyze the mutational spectrum of the phenylalanine hydroxylase (PAH) gene in phenylketonuria (PKU) patients in Northwest China, to identify mutational hot spots, and to determine the correlation between variants and clinical phenotypes of PKU. A large cohort of 475 PKU families in Northwest China was enrolled to analyze PAH gene variants using Sanger sequencing, Multiplex ligation-dependent probe amplification (MLPA), and gap-PCR. Bioinformatics software was used to predict the pathogenicity of novel variants and analyze the correlations between PAH gene variants and phenotypes of PKU patients. Read More

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http://dx.doi.org/10.1007/s11011-019-0387-7DOI Listing
February 2019

Health screening strategies in Maghreb countries: Situation Analysis and perspectives.

Tunis Med 2018 Oct-Nov;96(10-11):688-695

Background: The aim of screening is to improve individual health through an early detection of diseases at a stage where the prognosis of disease could be significantly. However, this kind of intervention is costly and it's necessary to respect criteria in selection of targeted diseases and screening tests.

Objective: The objective of this study was to describe public health screening policy in the Maghreb countries in order to identify the main barriers to the development of this type of intervention. Read More

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February 2019
1 Read

Amino acid disorders.

Ann Transl Med 2018 Dec;6(24):471

Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Human utilize 21 different amino acids; most of these can be synthesized endogenously, but 9 are "essential" in that they must be ingested in the diet. Read More

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http://dx.doi.org/10.21037/atm.2018.12.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331359PMC
December 2018

The effect of PKU diet on the maternal quality of life and social discrimination in relation to their educational status and place of living.

J Pediatr Endocrinol Metab 2019 Feb 7. Epub 2019 Feb 7.

Institute Child of Health, Inborn Errors of Metabolism, Athens, Greece.

Background Phenylketonuria (PKU) is an inherited metabolic disorder characterized by high levels of phenylalanine in the blood and brain, resulting in mental retardation, etc. Dietary treatment with low phenylalanine is the common treatment for this disease. Patients with other metabolic disorders, such as diabetes mellitus, were reported to have a higher percentage of quality-of-life damage (QLD) and social discriminations (SDs). Read More

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http://dx.doi.org/10.1515/jpem-2018-0525DOI Listing
February 2019

Age-Specific Cut-off Values of Amino Acids and Acylcarnitines for Diagnosis of Inborn Errors of Metabolism Using Liquid Chromatography Tandem Mass Spectrometry.

Biomed Res Int 2019 6;2019:3460902. Epub 2019 Jan 6.

Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka 1212, Bangladesh.

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is used for the diagnosis of more than 30 inborn errors of metabolisms (IEMs). Accurate and reliable diagnosis of IEMs by quantifying amino acids (AAs) and acylcarnitines (ACs) using LC-MS/MS systems depend on the establishment of age-specific cut-offs of the analytes. This study aimed to (1) determine the age-specific cut-off values of AAs and ACs in Bangladesh and (2) validate the LC-MS/MS method for diagnosis of the patients with IEMs. Read More

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http://dx.doi.org/10.1155/2019/3460902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339774PMC
January 2019

Efficacy and safety of sapropterin dihydrochloride in patients with phenylketonuria: A meta-analysis of randomized controlled trials.

Br J Clin Pharmacol 2019 Feb 5. Epub 2019 Feb 5.

Department of Pharmacy, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, P.R. China.

Aims: The aim of the present meta-analysis was to evaluate the efficacy and safety of sapropterin dihydrochloride in phenylketonuria (PKU) patients.

Methods: The following databases were searched for randomized controlled trials (RCT) regarding PKU patients treated with sapropterin dihydrochloride: Pubmed, Embase, Cochrane Library and clinicaltrials. Two authors independently selected studies, assessed the risk of bias and extracted data. Read More

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http://dx.doi.org/10.1111/bcp.13886DOI Listing
February 2019
2 Reads

Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria.

J Inherit Metab Dis 2019 Feb 1. Epub 2019 Feb 1.

Department of Pediatrics, Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg, Heidelberg, Germany.

Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38. Read More

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http://dx.doi.org/10.1002/jimd.12049DOI Listing
February 2019

Weaning practices in phenylketonuria vary between health professionals in Europe.

Mol Genet Metab Rep 2019 Mar 25;18:39-44. Epub 2018 Nov 25.

Birmingham Women's and Children's Hospital, Birmingham, UK.

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Read More

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http://dx.doi.org/10.1016/j.ymgmr.2018.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349955PMC
March 2019
1 Read

The neurological and psychological phenotype of adult patients with early-treated phenylketonuria: a systematic review.

J Inherit Metab Dis 2019 Jan 28. Epub 2019 Jan 28.

Division of Inborn Metabolic Diseases, Department of Paediatrics, University Hospital, Padua, Italy.

Newborn screening for phenylketonuria and early introduction of dietary therapy has been remarkably successful in preventing the severe neurological features of phenylketonuria, including mental retardation and epilepsy. However, concerns remain that long-term outcome is still suboptimal, particularly in adult patients who are no longer on strict phenylalanine-restricted diets. With our systematic literature review we aimed to describe the neurological phenotype of adults with early-treated phenylketonuria (ETPKU). Read More

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http://dx.doi.org/10.1002/jimd.12065DOI Listing
January 2019
2 Reads

Whole-exome sequencing as a powerful tool for identifying genetic causes in a patient with POLG-related disorders and phenylketonuria.

J Int Med Res 2019 Jan 24:300060518823096. Epub 2019 Jan 24.

2 Department of Newborn Screening, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing, China.

Objective: This study's aim was to identify the genetic causes in a patient with phenylketonuria and hearing loss, liver disease, developmental and mental retardation, hypotonia, and external ophthalmoplegia.

Methods: Whole-exome sequencing and Sanger sequencing analysis were used to determine the genetic causes of manifestations in a young boy with hearing loss, liver disease, develop-mental and mental retardation, hypotonia, and external ophthalmoplegia.

Results: We found that the child harbored polymerase gamma ( POLG) compound heterozygous mutations, c. Read More

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http://journals.sagepub.com/doi/10.1177/0300060518823096
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http://dx.doi.org/10.1177/0300060518823096DOI Listing
January 2019
5 Reads

The phenylketonuria-associated substitution R68S converts phenylalanine hydroxylase to a constitutively active enzyme but reduces its stability.

J Biol Chem 2019 Jan 23. Epub 2019 Jan 23.

Biochemistry, University of Texas Health Science Center, United States.

The naturally occuring R68S substitution of phenylalanine hydroxylase (PheH) causes phenylketonuria (PKU). However, the molecular basis for how the R68S variant leads to PKU remains unclear. Kinetic characterization of R68S PheH establishes that the enzyme is fully active in the absence of allosteric binding of phenylalanine, in contrast to the wild-type enzyme. Read More

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http://dx.doi.org/10.1074/jbc.RA118.006477DOI Listing
January 2019
2 Reads

Health utilities and parental quality of life effects for three rare conditions tested in newborns.

J Patient Rep Outcomes 2019 Jan 22;3(1). Epub 2019 Jan 22.

Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan Medical School, 300 North Ingalls Building, Ann Arbor, MI, 48109, USA.

Background: Measurement of health utilities is required for economic evaluations. Few studies have evaluated health utilities for rare conditions; even fewer have incorporated disutility that may be experienced by caregivers. This study aimed to (1) estimate health utilities for three rare conditions currently recommended for newborn screening at the state or federal level, and (2) estimate the disutility, or spillover, experienced by parents of patients diagnosed with a rare, heritable disorder. Read More

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https://jpro.springeropen.com/articles/10.1186/s41687-019-00
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http://dx.doi.org/10.1186/s41687-019-0093-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342747PMC
January 2019
5 Reads

Genotypes of 2579 patients with phenylketonuria reveal a high rate of BH4 non-responders in Russia.

PLoS One 2019 22;14(1):e0211048. Epub 2019 Jan 22.

Laboratory of DNA-diagnostics, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moscow, Russia.

Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). Furthermore, numerous studies on BH4-sensitive PAH deficiency have been conducted. To date, BH4, a cofactor of PAH, has not been used to treat PKU in Russia. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211048PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342299PMC
January 2019

Toward mechanistic models for genotype-phenotype correlations in phenylketonuria using protein stability calculations.

Hum Mutat 2019 Jan 16. Epub 2019 Jan 16.

The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Phenylketonuria (PKU) is a genetic disorder caused by variants in the gene encoding phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine to neurotoxic levels. Here, we analyzed the cellular stability, localization, and interaction with wild-type PAH of 20 selected PKU-linked PAH protein missense variants. Several were present at reduced levels in human cells, and the levels increased in the presence of a proteasome inhibitor, indicating that proteins are proteasome targets. Read More

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http://dx.doi.org/10.1002/humu.23707DOI Listing
January 2019
2 Reads

Identification and characterization of a sterically robust phenylalanine ammonia-lyase among 481 natural isoforms through association of in silico and in vitro studies.

Enzyme Microb Technol 2019 Mar 12;122:36-54. Epub 2018 Dec 12.

Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

The enzyme phenylalanine ammonia lyase (PAL) is of special importance for the treatment of phenylketonuria patients. The aim of this study was to find a stable recombinant PAL with suitable kinetic properties among all natural PAL producing species using in silico and experimental approaches. To find such a stable PAL among 481 natural isoforms, 48,000 of 3-D models were predicted using the Modeller 9. Read More

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http://dx.doi.org/10.1016/j.enzmictec.2018.12.006DOI Listing
March 2019
2 Reads

Phenylalanine and tyrosine measurements across gestation by tandem mass spectrometer on dried blood spot cards from normal pregnant women.

Genet Med 2019 Jan 10. Epub 2019 Jan 10.

Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, 43205, USA.

Purpose: Maternal phenylketonuria (MPKU) requires strict control of phenylalanine (Phe) and supplemental tyrosine (Tyr). Monitoring during pregnancy using dried blood spot (DBS) cards by tandem mass spectrometry (MS/MS) is now standard practice, however there are no Phe and Tyr reference ranges for DBS MS/MS method in healthy pregnant women.

Methods: DBS cards (63-1364 days in storage) from healthy women with singleton pregnancies were analyzed by MS/MS. Read More

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http://dx.doi.org/10.1038/s41436-018-0407-8DOI Listing
January 2019

The Role of Technology in Newborn Screening.

N C Med J 2019 Jan-Feb;80(1):49-53

professor emeritus of pediatrics, Medical Genetics Division, Duke University Medical Center, Durham, North Carolina

This commentary traces the expansion of newborn screening for inherited metabolic disorders during the past 55 years, from the first simple test for phenylketonuria to the current panel of over 35 conditions. Emphasis is placed on the role played by technology and the contributions made by researchers in North Carolina. Read More

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http://dx.doi.org/10.18043/ncm.80.1.49DOI Listing
January 2019

Severe acute pancreatitis in a child with phenylketonuria.

Arch Pediatr 2019 Feb 6;26(2):115-117. Epub 2019 Jan 6.

Neonatology department, Le Havre Hospital, BP 24, 76083 Le Havre cedex, France.

We report for the first time severe acute pancreatitis in a child treated for phenylketonuria (PKU) discovered on neonatal screening. This 2-year-old boy was first hospitalized for bilious vomiting and moderate back pain. Laboratory values included a lipase level of 1. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0929693X183026
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http://dx.doi.org/10.1016/j.arcped.2018.12.003DOI Listing
February 2019
5 Reads

Nutritional management of phenylalanine hydroxylase (PAH) deficiency in pediatric patients in Canada: a survey of dietitians' current practices.

Orphanet J Rare Dis 2019 Jan 8;14(1). Epub 2019 Jan 8.

McMaster Children's hospital, Hamilton, Ontario, Canada.

Background: Phenylalanine hydroxylase (PAH) deficiency is one of 31 targeted inherited metabolic diseases (IMD) for the Canadian Inherited Metabolic Diseases Research Network (CIMDRN). Early diagnosis and initiation of treatment through newborn screening has gradually shifted treatment goals from the prevention of disabling complications to the optimization of long term outcomes. However, clinical evidence demonstrates that subtle suboptimal neurocognitive outcomes are present in the early and continuously diet-treated population with PAH deficiency. Read More

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http://dx.doi.org/10.1186/s13023-018-0978-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323774PMC
January 2019

Screening and development of enzymes for determination and transformation of amino acids.

Authors:
Yasuhisa Asano

Biosci Biotechnol Biochem 2019 Jan 8:1-15. Epub 2019 Jan 8.

a Biotechnology Research Center and Department of Biotechnology , Toyama Prefectural University , Imizu , Toyama , Japan.

The high stereo- and substrate specificities of enzymes have been utilized for micro-determination of amino acids. Here, I review the discovery of l-Phe dehydrogenase and its practical use in the diagnosis of phenylketonuria in more than 5,400,000 neonates over two decades in Japan. Screening and uses of other selective enzymes for micro-determination of amino acids have also been discussed. Read More

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https://www.tandfonline.com/doi/full/10.1080/09168451.2018.1
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http://dx.doi.org/10.1080/09168451.2018.1559027DOI Listing
January 2019
4 Reads

A comprehensive multiplex PCR based exome-sequencing assay for rapid bloodspot confirmation of inborn errors of metabolism.

BMC Med Genet 2019 Jan 6;20(1). Epub 2019 Jan 6.

Children and Women's Hospital of Shanxi, Women Health Center of Shanxi, Taiyuan, Shanxi, China.

Background: Tandem mass spectrometry (MS MS) and simple fluorometric assays are currently used in newborn screening programs to detect inborn errors of metabolism (IEM). The aim of the study was to evaluate the clinical utility of exome sequencing as a second tier screening method to assist clinical diagnosis of the newborn.

Methods: A novel PCR-exome amplification and re-sequencing (PEARS) assay was designed and used to detect mutations in 122 genes associated with 101 IEM. Read More

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http://dx.doi.org/10.1186/s12881-018-0731-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322297PMC
January 2019
3 Reads

Development of national consensus statements on food labelling interpretation and protein allocation in a low phenylalanine diet for PKU.

Orphanet J Rare Dis 2019 Jan 3;14(1). Epub 2019 Jan 3.

Dietetic Department, Birmingham Women's & Children's NHS Foundation Trust, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.

Background: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients.

Methodology: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0950-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318866PMC
January 2019
2 Reads
3.358 Impact Factor

RNA-Seq analysis in an avian model of maternal phenylketonuria.

Mol Genet Metab 2019 Jan 6;126(1):23-29. Epub 2018 Sep 6.

Department of Biology, University of Central Oklahoma, Edmond, OK, USA. Electronic address:

Cardiac malformations (CVMs) are a leading cause of infant morbidity and mortality. CVMs are particularly prevalent when the developing fetus is exposed to high levels of phenylalanine in-utero in mothers with Phenylketonuria. Yet, elucidating the underlying molecular mechanism leading to CVMs has proven difficult. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183025
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http://dx.doi.org/10.1016/j.ymgme.2018.09.003DOI Listing
January 2019
5 Reads

Neurocognitive functioning in adults with phenylketonuria: Report of a 10-year follow-up.

Mol Genet Metab 2018 Dec 26. Epub 2018 Dec 26.

University of Münster, Department of Pediatrics, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.

Background: The long-term prognosis of early treated phenylketonuria (PKU) is still under discussion. Aim of this controlled long-term study was to assess the neurological and neuropsychological outcome in adult patients with early-treated PKU.

Methods: We investigated 35 patients with early-treated classical PKU aged 29 to 51 years (mean age 41 years) and 18 healthy controls matched for age and socioeconomic status. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183060
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http://dx.doi.org/10.1016/j.ymgme.2018.12.011DOI Listing
December 2018
5 Reads

Sensitive determination of monoamine neurotransmitters, their main metabolites and precursor amino acids in different mouse brain components by liquid chromatography-electrospray tandem mass spectrometry after selective sample clean-up.

Biomed Chromatogr 2018 Dec 29:e4479. Epub 2018 Dec 29.

Section for Forensic Chemistry, Department of Forensic Medicine, Aarhus University, Aarhus N, Denmark.

For the assessment of diets and supplements formulated for the treatment of phenylketonuria, a highly sensitive and selective method was developed and validated for the quantification of dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), phenylalanine, tyrosine and tryptophan in mouse cerebellum, brain stem, hypothalamus, parietal cortex, anterior piriform cortex and bulbus olfactorius. Samples were extracted by deproteinization with acetonitrile, and the extracts were cleaned up by strong anion exchange and weak cation exchange applied sequentially. The substances were detected by rapid liquid chromatography tandem mass spectrometry. Read More

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http://dx.doi.org/10.1002/bmc.4479DOI Listing
December 2018

Conformational selection turns on phenylalanine hydroxylase.

J Biol Chem 2018 Dec;293(51):19544-19545

From the Department of Chemistry, Center of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong

Phenylalanine hydroxylase catalyzes a critical step in the phenylalanine catabolic pathway, and impairment of the human enzyme is linked to phenylketonuria. Phenylalanine is also a positive allosteric regulator of the enzyme, and the allosteric binding site has been determined by crystallography. However, the allosteric activation mechanism remains unclear. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.H118.006676
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http://dx.doi.org/10.1074/jbc.H118.006676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314130PMC
December 2018
4 Reads
4.573 Impact Factor

Construction of liquid crystal-based sensing platform for sensitive and selective detection of L-phenylalanine based on alkaline phosphatase.

Langmuir 2018 Dec 21. Epub 2018 Dec 21.

The detection of L-phenylalanine (L-Phe) has become one of most pressing issues concerning diagnosis and treatment of phenylketonuria in neonates, yet a simple and robust methodology has yet to be developed. Here the application of novel liquid crystals (LCs) sensing platform for sensitive, selective, and label-free detection of L-Phe was reported at the first time. We devised a strategy to fabricate the sodium monododecyl phosphate (SMP) decorated LC sensing platform with the appearance of dark. Read More

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http://dx.doi.org/10.1021/acs.langmuir.8b03682DOI Listing
December 2018
1 Read

Protocol for psychosocial screening of adolescents and young adults with chronic illness.

Intern Med J 2018 Dec 18. Epub 2018 Dec 18.

Mater Young Adult Health Centre, Mater Health, Brisbane, Australia, 4101.

Background: One in five adolescents and young adults (AYAs) have a chronic health condition necessitating on-going engagement with health care systems. Despite increasing prevalence there remains limited understanding of the burden of illness they experience. Living with a chronic illness can challenge healthy adolescent development, with the unique health and developmental issues affecting AYAs requiring different responses from the health care system. Read More

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http://doi.wiley.com/10.1111/imj.14211
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http://dx.doi.org/10.1111/imj.14211DOI Listing
December 2018
6 Reads

Parental awareness of newborn bloodspot screening in Ireland.

Ir J Med Sci 2018 Dec 15. Epub 2018 Dec 15.

Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity (4i), University of Limerick, Limerick, Ireland.

Background: There is little known regarding how familiar parents are with the newborn bloodspot screening (NBS) test or how well parents of a child with a screen-detected condition understand that condition initially.

Aim: The study aim was to examine parental NBS awareness and conditions screened.

Methods: Two studies were conducted: [1] Parents of children with cystic fibrosis (CF) detected via NBS and subsequently, diagnosed (n = 124) completed a telephone questionnaire regarding information they received at the time of NBS. Read More

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http://link.springer.com/10.1007/s11845-018-1949-0
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http://dx.doi.org/10.1007/s11845-018-1949-0DOI Listing
December 2018
12 Reads

Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria.

Genet Med 2018 Dec 14. Epub 2018 Dec 14.

Departments of Molecular and Medical Genetics and Pediatrics, Oregon Health & Science University, Portland, OR, USA.

Purpose: Phenylketonuria (PKU) is a rare metabolic disorder that requires life-long management to reduce phenylalanine (Phe) concentrations within the recommended range. The availability of pegvaliase (PALYNZIQ™, an enzyme that can metabolize Phe) as a new therapy necessitates the provision of guidance for its use.

Methods: A Steering Committee comprising 17 health-care professionals with experience in using pegvaliase through the clinical development program drafted guidance statements during a series of face-to-face meetings. Read More

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http://dx.doi.org/10.1038/s41436-018-0403-zDOI Listing
December 2018
3 Reads

Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study.

Nutrients 2018 Dec 7;10(12). Epub 2018 Dec 7.

Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany.

Children with phenylketonuria (PKU) follow a protein restricted diet with negligible amounts of docosahexaenoic acid (DHA). Low DHA intakes might explain subtle neurological deficits in PKU. We studied whether a DHA supply modified plasma DHA and neurological and intellectual functioning in PKU. Read More

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http://dx.doi.org/10.3390/nu10121944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316534PMC
December 2018
3.148 Impact Factor

Transient phenylketonuria in premature infants.

Nutrition 2019 Mar 20;59:180-181. Epub 2018 Aug 20.

Department of Pediatrics, Hospital Universitario Rio Hortega, Valladolid, Spain.

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (phe) metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase that converts phe into tyrosine. If left untreated, PKU results in increased phe concentrations in the blood and in the brain, which cause severe intellectual disability, epilepsy, and behavioral problems. These disorders can be prevented if a diet low in phe is introduced. Read More

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http://dx.doi.org/10.1016/j.nut.2018.08.013DOI Listing
March 2019
2 Reads

[Characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2018 Dec;35(6):791-795

Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, China.

Objective: To explore the characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province.

Methods: The 13 exons of the PAH gene were subjected to PCR amplification and direct sequencing. Large fragment deletion and duplication of the PAH gene were detected with a multiple ligation-dependent probe amplification (MLPA) assay. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2018.06.003DOI Listing
December 2018
7 Reads

A comprehensive in silico characterization of bacterial signal peptides for the excretory production of phenylalanine ammonia lyase in .

3 Biotech 2018 Dec 16;8(12):488. Epub 2018 Nov 16.

1Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

double mutant (C503S/C565S) phenylalanine ammonia-lyase (PAL) is an appealing enzyme in the enzyme-replacement therapy of phenylketonuria. Yet abundant production of this enzyme has been of concern for industrial production. In this study, we have characterized 1175 bacterial signal peptides (SPs) and identified the most efficient ones for the excretory production of mutant AvPAL. Read More

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http://dx.doi.org/10.1007/s13205-018-1517-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240017PMC
December 2018

Mutational and phenotypic spectrum of phenylalanine hydroxylase deficiency in Zhejiang Province, China.

Sci Rep 2018 Nov 20;8(1):17137. Epub 2018 Nov 20.

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Phenylalanine hydroxylase deficiency (PAHD), one of the genetic disorders resulting in hyperphenylalaninemia, has a complex phenotype with many variants and genotypes among different populations. Here, we describe the mutational and phenotypic spectrum of PAHD in a cohort of 420 patients from neonatal screening between 1999 and 2016. The observed phenotypes comprised 43. Read More

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http://www.nature.com/articles/s41598-018-35373-9
Publisher Site
http://dx.doi.org/10.1038/s41598-018-35373-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244417PMC
November 2018
4 Reads
5.078 Impact Factor

The Use of Glycomacropeptide in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis.

Nutrients 2018 Nov 18;10(11). Epub 2018 Nov 18.

Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal.

In phenylketonuria (PKU), synthetic protein derived from L-amino acids (AAs) is essential in a low-phenylalanine (Phe) diet. Glycomacropeptide (GMP), an intact protein, is very low in Phe in its native form. It has been modified and adapted for PKU to provide an alternative protein source through supplementation with rate-limiting amino acids (GMP-AAs), although it still contains residual Phe. Read More

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http://www.mdpi.com/2072-6643/10/11/1794
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http://dx.doi.org/10.3390/nu10111794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266274PMC
November 2018
6 Reads
3.150 Impact Factor

Reproductive experience of women living with phenylketonuria.

Mol Genet Metab Rep 2018 Dec 2;17:64-68. Epub 2018 Nov 2.

Birmingham Women's & Children's NHS Trust, Birmingham, United Kingdom.

Introduction: Many women with PKU are well-informed about the risks of maternal PKU but there are several barriers to achieving satisfactory metabolic control before and during pregnancy. Many studies have documented the outcome of maternal PKU infants, but very little has been reported about the experiences of women of reproductive age with PKU, particularly about their psychosexual development, pre-conception, pregnancy and postnatal experience.

Methods: In the UK, in a subsection of an online questionnaire conducted by the National Society for PKU (NSPKU) about living with PKU, women aged 18 years and over completed 9 closed questions about their pre-conception, pregnancy and post-natal experiences and an open-ended question on their reproductive health. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22144269183008
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http://dx.doi.org/10.1016/j.ymgmr.2018.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218656PMC
December 2018
12 Reads

A comprehensive study of phenylalanine hydroxylase gene mutations in the Iranian phenylketonuria patients.

Eur J Med Genet 2018 Oct 30. Epub 2018 Oct 30.

Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, IR, Iran. Electronic address:

Phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene. After thalassemia, PKU is considered as the most common autosomal recessive diseases in the Iranian population. Therefore, an efficient diagnostic strategy is required to identify disease-causing mutations in this population. Read More

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http://dx.doi.org/10.1016/j.ejmg.2018.10.011DOI Listing
October 2018
2 Reads
1.490 Impact Factor

Behavioral and Emotional Problems in Early-Treated Brazilian Children and Adolescents with Phenylketonuria.

Med Sci Monit 2018 Oct 30;24:7759-7769. Epub 2018 Oct 30.

Institute of Childcare and Pediatrics "Martagão Gesteira", Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

BACKGROUND Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene. When untreated, PKU leads to a significant intellectual deficiency. Although early initiation of dietary therapy allows normal cognitive development, low adherence to treatment may result in neuropsychological deficits, including attention problems. Read More

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https://www.medscimonit.com/abstract/index/idArt/909146
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http://dx.doi.org/10.12659/MSM.909146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354646PMC
October 2018
16 Reads

One-year follow-up of B vitamin and Iron status in patients with phenylketonuria provided tetrahydrobiopterin (BH4).

Orphanet J Rare Dis 2018 Oct 30;13(1):192. Epub 2018 Oct 30.

Department of Human Genetics, Metabolic Nutrition Program, Emory University School of Medicine, Atlanta, GA, USA.

Background: People with Phenylketonuria (PKU) who respond to tetrahydrobiopterin (BH4) often decrease dependence on medical food (MF) following increased phenylalanine (phe) tolerance. Responders to BH4 may experience a reduction in certain nutrients if not compensated through intact foods or supplements. This study investigated B6, B12, folate, and iron status based on blood levels and dietary intake in patients with PKU responsive to BH4 over 1 year. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0923-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206913PMC
October 2018
6 Reads

White matter microstructural damage in early treated phenylketonuric patients.

Orphanet J Rare Dis 2018 Oct 26;13(1):188. Epub 2018 Oct 26.

Neuropediatric Department, PKU Follow Up Unit, Hospital Sant Joan de Déu (HSJD), Institut de Recerca Sant Joan de Deu (IRSJD), Passeig Sant Joan de Deu 2, Postal code, 08950, Barcelona, Spain.

Background: Despite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)).

Methods: DTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Read More

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https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0
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http://dx.doi.org/10.1186/s13023-018-0912-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203973PMC
October 2018
14 Reads