7,837 results match your criteria Phenylketonuria


Can the Microbiome Deliver? A Proof-of-Concept Engineered E. coli PKU Therapeutic.

Cell Host Microbe 2019 Apr;25(4):473-474

Department of Natural Sciences, University of Michigan Dearborn, Dearborn, MI 48128, USA. Electronic address:

Phenylketonuria (PKU) is a rare genetic disorder that causes phenylalanine toxicity in the brain. Two studies, Crook et al. (2019), in this issue of Cell Host & Microbe, and Isabella et al. Read More

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http://dx.doi.org/10.1016/j.chom.2019.03.015DOI Listing
April 2019
1 Read

The evaluation of phenylalanine levels in Estonian phenylketonuria patients during eight years by electronic laboratory records.

Mol Genet Metab Rep 2019 Jun 23;19:100467. Epub 2019 Mar 23.

Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.

Blood phenylalanine (Phe) values from the dried blood spots of all Estonian phenylketonuria (PKU) patients have been deposited into a unified electronic laboratory database for eight years, providing an opportunity to assess the adherence of the patients to dietary recommendations over time and to observe patient practices both individually and collectively. Our results demonstrate generally good adherence to clinical and dietary recommendations during the first six years of life, as the percentage of patients with median Phe values fitting under the national recommendation levels were 95%, 84% and 70% in age groups 0-1, 1-2 and 2-6 years, respectively. Conversely, significant deviations occur in the group of 6 to 12 year-olds, mildly decreasing in adolescence and increasing in adulthood (43%, 53% and 57%, respectively). Read More

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http://dx.doi.org/10.1016/j.ymgmr.2019.100467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434493PMC

Asymmetric dimethylarginine as a potential biomarker for management and follow-up of phenylketonuria.

Eur J Pediatr 2019 Apr 2. Epub 2019 Apr 2.

Group of Metabolism, Biocruces Bizkaia Health Research Institute, CIBER de Enfermedades Raras (CIBERER), Plaza de Cruces 12, 48903, Barakaldo, Spain.

Phenylketonuria's (PKU) treatment based on low-protein diet may affect other metabolic pathways, such as that of asymmetric dimethylarginine (ADMA). The aim of this study was to evaluate the reliability of ADMA as a biomarker of adequate metabolic control and possible nutritional risk in a long-term PKU patient population. One hundred and six dietary-treated PKU patients from four hospitals in Spain were enrolled in this cross-sectional study. Read More

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http://dx.doi.org/10.1007/s00431-019-03365-0DOI Listing

Case Report: Neuropsychiatric Symptoms in PKU Disease.

J Pediatr Health Care 2019 Mar 28. Epub 2019 Mar 28.

Phenylketonuria is a rare inborn error of metabolism. The build-up of phenylalanine in the blood and body tissues can have significant impact on the brain's development. High phenylalanine levels have been shown to be associated with an increase in neuropsychiatric symptoms, including mood, anxiety, and attention problems; decreased social competence; and low self-esteem. Read More

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http://dx.doi.org/10.1016/j.pedhc.2019.02.007DOI Listing
March 2019
1 Read

Adaptive Strategies of the Candidate Probiotic E. coli Nissle in the Mammalian Gut.

Cell Host Microbe 2019 Apr 26;25(4):499-512.e8. Epub 2019 Mar 26.

Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Probiotics are living microorganisms that are increasingly used as gastrointestinal therapeutics by virtue of their innate or engineered genetic function. Unlike abiotic therapeutics, probiotics can replicate in their intended site, subjecting their genomes and therapeutic properties to natural selection. We exposed the candidate probiotic E. Read More

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http://dx.doi.org/10.1016/j.chom.2019.02.005DOI Listing

6-Pyruvoyltetrahydropterin Synthase Deficiency: Review and Report of 28 Arab Subjects.

Pediatr Neurol 2019 Feb 18. Epub 2019 Feb 18.

Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia; King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Electronic address:

Background: Tetrahydrobiopterin is an essential cofactor for the hydroxylation of aromatic amino acids phenylalanine, tyrosine, and tryptophan. Therefore, tetrahydrobiopterin deficiency results in hyperphenylalaninemia as well as dopamine and serotonin depletion in the central nervous system. The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes the second step of de novo synthesis of tetrahydrobiopterin, and its deficiency is the most frequent cause of tetrahydrobiopterin metabolism disorders. Read More

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http://dx.doi.org/10.1016/j.pediatrneurol.2019.02.008DOI Listing
February 2019
1.504 Impact Factor

Phase I clinical evaluation of CNSA-001 (sepiapterin), a novel pharmacological treatment for phenylketonuria and tetrahydrobiopterin deficiencies, in healthy volunteers.

Mol Genet Metab 2019 Feb 10. Epub 2019 Feb 10.

Dietmar-Hopp-Metabolic Center, University Children's Hospital, Heidelberg, Germany; Division of Metabolism, University Children's Hospital, Zurich, Switzerland. Electronic address:

Tetrahydrobiopterin (BH) is the natural cofactor of aromatic amino acid hydroxylases and essential for degradation of phenylalanine and synthesis of catecholamines and serotonin. It can be synthesized either de novo from GTP or through the salvage pathway from sepiapterin. Sepiapterin, a natural precursor of BH, is a more stable molecule and is transported more efficiently across cellular membranes, thus having potentially significant advantage over BH as a pharmacological agent for diseases associated with BH-deficient conditions. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.02.001DOI Listing
February 2019
1 Read

Diversity of phenylalanine tolerance in pregnant phenylketonuria patients homozygous for the p.R408W mutation: the need for improved understanding of phenylalanine homeostasis.

J Biol Regul Homeost Agents 2019 Mar-Apr,;33(2):491-497

PKU Polyclinic, Institute of Mother and Child, Warsaw, Poland.

Dietetic treatment of phenylketonuria (PKU) includes a low-phenylalanine (phe) diet that provides sufficient phe for maintenance and growth plus special phe-free formulas with amino acids to meet requirements for protein, energy and micronutrients. Read More

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March 2019
2 Reads

The significant role of educational status in PKU patients: the beneficial effect of psychological support in depression.

Int J Adolesc Med Health 2019 Mar 19. Epub 2019 Mar 19.

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

Introduction Classical Phenylketonuria (PKU) is a metabolic disease characterized by high phenylalanine (phe) levels in blood and brain. PKU patients are commonly treated with low phe diet supplemented with amino acid free formula. High Phe levels minimize brain tryptophan concentration, the pressure of serotonin, which is responsible for the appearance of depression symptoms. Read More

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http://dx.doi.org/10.1515/ijamh-2018-0233DOI Listing

Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals.

Hum Genet 2019 Mar 18. Epub 2019 Mar 18.

Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.

Incidence rates of Mendelian diseases vary among ethnic groups, and frequencies of variant types of causative genes also vary among human populations. In this study, we examined to what extent we can predict population frequencies of recessive disorders from genomic data, and explored better strategies for variant interpretation and classification. We used a whole-genome reference panel from 3552 general Japanese individuals constructed by the Tohoku Medical Megabank Organization (ToMMo). Read More

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http://dx.doi.org/10.1007/s00439-019-01998-7DOI Listing
March 2019
3 Reads

Depletion of interfering IgG and IgM is critical to determine the role of IgE in pegvaliase-associated hypersensitivity.

J Immunol Methods 2019 May 14;468:20-28. Epub 2019 Mar 14.

BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.

Pegvaliase is an enzyme substitution therapy developed to lower blood phenylalanine (Phe) in adults with phenylketonuria (PKU). In phase 3 clinical studies, pegvaliase substantially reduced mean blood Phe in adult subjects with PKU. The most common type of adverse event observed in the pegvaliase clinical program was hypersensitivity adverse events (HAEs), which included occurrences of arthralgia, rash, and pruritis. Read More

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http://dx.doi.org/10.1016/j.jim.2019.03.004DOI Listing
May 2019
4 Reads
2.005 Impact Factor

Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU).

PLoS One 2019 15;14(3):e0213391. Epub 2019 Mar 15.

Molecular Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands.

Introduction: In phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213391PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420157PMC
March 2019
2 Reads

Acute effect of an amino acid mixture in the rat glycemic profile.

J Cell Biochem 2019 Mar 14. Epub 2019 Mar 14.

Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto, Porto, Portugal.

Amino acid mixtures (AAM) are protein substitutes used for phenylketonuria treatment, but their metabolic effects have not been well characterized. The objective of this study was to compare the acute glycemic response to free amino acids (free AA) from AAM with the response to intact protein (iProtein). Male Wistar rats (n = 14) were administered by gavage a bolus of free AA (n = 7) or iProtein as albumin (n = 7) containing equivalent amounts of nitrogen. Read More

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http://dx.doi.org/10.1002/jcb.28576DOI Listing
March 2019
1 Read

Phenylketonuria: Current Treatments and Future Developments.

Drugs 2019 Apr;79(5):495-500

Division Medical Genetics, Department of Pediatrics, University of Pittsburgh, School of Medicine, Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Phenylalanine hydroxylase (PAH) deficiency is an inborn error of metabolism that results in elevated phenylalanine levels in blood. The classical form of the disease with phenylalanine level > 1200 µmol/L in blood is called phenylketonuria (PKU) and is associated with severe intellectual disability when untreated. In addition, phenylalanine levels above the therapeutic range in pregnant female patients lead to adverse fetal effects. Read More

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http://dx.doi.org/10.1007/s40265-019-01079-zDOI Listing

Role of protein structure in variant annotation: structural insight of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency.

Pathology 2019 Apr 8;51(3):274-280. Epub 2019 Mar 8.

Department of Chemical Pathology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong. Electronic address:

Genetic defects on 6-pyruvoyl-tetrahydropterin synthase (PTPS) are the most prevalent cause of hyperphenylalaninaemia not due to phenylalanine hydrolyase deficiency (phenylketonuria). PTPS catalyses the second step of tetrahydrobiopterin (BH) cofactor biosynthesis, and its deficiency represents the most common form of BH deficiency. Untreated PTPS deficiency results in depletion of the neurotransmitters dopamine, catecholamine and serotonin causing neurological symptoms. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00313025183042
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http://dx.doi.org/10.1016/j.pathol.2018.11.011DOI Listing
April 2019
5 Reads

Growth, Protein and Energy Intake in Children with PKU Taking a Weaning Protein Substitute in the First Two Years of Life: A Case-Control Study.

Nutrients 2019 Mar 5;11(3). Epub 2019 Mar 5.

Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B4 6NH, UK.

Growth issues have been observed in young children with phenylketonuria (PKU), but studies are conflicting. In infancy, there is an increasing trend to introduce a second-stage semi-solid weaning protein substitute (WPS) but there is concern that this may not meet energy requirements. In this longitudinal, prospective study, 20 children with PKU transitioning to a WPS, and 20 non-PKU controls were observed monthly from weaning commencement (4⁻6 months) to 12 m and at 15, 18 and 24 months of age for: weight, length, head circumference, body mass index (BMI), energy and macronutrient intake. Read More

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http://dx.doi.org/10.3390/nu11030552DOI Listing
March 2019
3.148 Impact Factor

Studying the effect of large neutral amino acid supplements on oxidative stress in phenylketonuric patients.

J Pediatr Endocrinol Metab 2019 Mar;32(3):269-274

Division of Physiology, Harran University, Sanlıurfa, Turkey.

Background Oxidative stress may be one of the causes responsible for mental retardation in phenylketonuria (PKU) patients. Phenylalanine (Phe) reduces antioxidant defense and promotes oxidative stress by causing increase in reactive oxygen-nitrogen species. Our study aimed to investigate the effect of different treatments (amino acid mixture/large neutral amino acid [LNAA] supplements) on oxidative stress which are applied to late-diagnosed patients. Read More

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http://dx.doi.org/10.1515/jpem-2018-0454DOI Listing
March 2019
6 Reads

Genotype-phenotype correlations and BH estimated responsiveness in patients with phenylketonuria from Rio de Janeiro, Southeast Brazil.

Mol Genet Genomic Med 2019 Mar 3:e610. Epub 2019 Mar 3.

Serviço de Genética Médica, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Genetic heterogeneity and compound heterozygosis give rise to a continuous spectrum of phenylalanine hydroxylase deficiency and metabolic phenotypes in phenylketonuria (PKU). The most used parameters for evaluating phenotype in PKU are pretreatment phenylalanine (Phe) levels, tolerance for dietary Phe, and Phe overloading test. Phenotype can vary from a "classic" (severe) form to mild hyperphenylalaninemia, which does not require dietary treatment. Read More

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http://dx.doi.org/10.1002/mgg3.610DOI Listing

Emergence of visible light optical properties of L-phenylalanine aggregates.

PeerJ 2019 25;7:e6518. Epub 2019 Feb 25.

Vilnius University, Life Sciences Center, Institute of Biotechnology, Vilnius, Lithuania.

The ability of phenylalanine to form fibrillar nanostructures was demonstrated on multiple occasions, and such an oligomerization reaction could be the cause of cytotoxicity in patients with phenylketonuria. These findings were supported by claims that L-phenylalanine (Phe) fibrils have amyloid properties and can be detected using thioflavin T fluorescence assay. However, a part of Phe aggregation studies reported the opposite data, suggesting no amyloid structures to be formed. Read More

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http://dx.doi.org/10.7717/peerj.6518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394350PMC
February 2019
3 Reads

How Does Feeding Development and Progression onto Solid Foods in PKU Compare with Non-PKU Children During Weaning?

Nutrients 2019 Feb 28;11(3). Epub 2019 Feb 28.

Birmingham Women's and Children's Hospital NHS Foundation Trust, Birmingham B4 6NH, UK.

Weaning is complex for children with phenylketonuria (PKU). Breastmilk/infant formula and phenylalanine (Phe)-free infant protein-substitute (PS) are gradually replaced with equivalent amounts of Phe-containing food, a semi-solid/spoonable weaning PS and special low-protein foods. In PKU, feeding patterns/practices during weaning in PKU have not been formally evaluated. Read More

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http://dx.doi.org/10.3390/nu11030529DOI Listing
February 2019
3.148 Impact Factor

The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial.

Nutrients 2019 Feb 28;11(3). Epub 2019 Feb 28.

Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK.

In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Read More

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http://dx.doi.org/10.3390/nu11030520DOI Listing
February 2019
1 Read
3.148 Impact Factor

The effects of low protein products availability on growth parameters and metabolic control in selected amino acid metabolism disorders patients.

Int J Pediatr Adolesc Med 2018 Jun 14;5(2):60-68. Epub 2018 Jun 14.

Biostatistics Epidemiology & Scientific Computing Department, King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, SA, USA.

Background: In Saudi Arabia, a diet for life policy has been adopted in the management of amino acid metabolism disorders for years. However, the specially designed low protein products/medical foods - which are one of the important treatment tools - were not available up until several years ago in Saudi Arabia (SA). Our aim was to measure the compliance and quality of life in patients affected with these disorders followed in the metabolic nutrition clinic at King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, SA. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23526467183003
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http://dx.doi.org/10.1016/j.ijpam.2018.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363253PMC
June 2018
2 Reads

Medical care of patients with disorders of aromatic amino acid metabolism: a report based on the Polish National Health Fund data records.

Pediatr Endocrinol Diabetes Metab 2018 ;2018(3):118-125

Introduction: Patients with disorders of aromatic amino acid metabolism are a heterogeneous group. They vary in morbidity and medical care requirements. Polish newborn screening program allows for quick diagnosis of some inborn errors of metabolism (such as classical phenylketonuria, mild hyperphenylalaninemias, tyrosinemia type 1 and tyrosinemia type 2) and subsequent immediate treatment. Read More

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http://dx.doi.org/10.5114/pedm.2018.80993DOI Listing
January 2018

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

Clin Drug Investig 2019 Apr;39(4):379-384

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
April 2019
1 Read

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

Orphanet J Rare Dis 2019 02 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377744PMC
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
9 Reads

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 Mar;32(3):281-285

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

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, 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
5 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://doi.wiley.com/10.1002/jimd.12049
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http://dx.doi.org/10.1002/jimd.12049DOI Listing
February 2019
10 Reads

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
2 Reads

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

J Inherit Metab Dis 2019 Mar;42(2):209-219

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

Newborn screening for phenylketonuria (PKU) and early introduction of dietary therapy has been remarkably successful in preventing the severe neurological features of PKU, 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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https://onlinelibrary.wiley.com/doi/abs/10.1002/jimd.12065
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http://dx.doi.org/10.1002/jimd.12065DOI Listing
March 2019
10 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 Mar 24;47(3):1387-1394. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421386PMC
March 2019
10 Reads

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

J Biol Chem 2019 Mar 23;294(12):4359-4367. Epub 2019 Jan 23.

From the Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, Texas 78229 and

The naturally occurring 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 WT enzyme. Read More

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http://dx.doi.org/10.1074/jbc.RA118.006477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433070PMC
March 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
11 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
2 Reads

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

Hum Mutat 2019 Apr 25;40(4):444-457. Epub 2019 Jan 25.

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
April 2019
4 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
3 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
2 Reads

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
11 Reads

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

Orphanet J Rare Dis 2019 01 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
4 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 01 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
3 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
7 Reads

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

Mol Genet Metab 2019 Mar 26;126(3):246-249. 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
March 2019
10 Reads