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    Intronic PAH gene mutations cause a splicing defect by a novel mechanism involving U1snRNP binding downstream of the 5' splice site.
    PLoS Genet 2018 Apr 23;14(4):e1007360. Epub 2018 Apr 23.
    Centro de Biología Molecular Severo Ochoa UAM-CSIC, CEDEM, CIBERER, IdiPaz, Universidad Autónoma, Madrid, Spain.
    Phenylketonuria (PKU), one of the most common inherited diseases of amino acid metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Recently, PAH exon 11 was identified as a vulnerable exon due to a weak 3' splice site, with different exonic mutations affecting exon 11 splicing through disruption of exonic splicing regulatory elements. In this study, we report a novel intron 11 regulatory element, which is involved in exon 11 splicing, as revealed by the investigated pathogenic effect of variants c. Read More

    Parenting a Child with Phenylketonuria: An Investigation into the Factors That Contribute to Parental Distress.
    JIMD Rep 2018 Apr 20. Epub 2018 Apr 20.
    School of Psychology, Cardiff University, Cardiff, UK.
    Phenylketonuria (PKU) is an inherited metabolic condition that can lead to the onset of intellectual disabilities if not strictly managed through a low-protein diet. Parents are responsible for supervising their child's treatment for PKU, which may impact on their experience of distress. This cross-sectional study aimed to identify the factors that contribute to distress in parents who care for a child with PKU, distinct from parents in the general population. Read More

    A new therapy prevents intellectual disability in mouse with phenylketonuria.
    Mol Genet Metab 2018 Apr 7. Epub 2018 Apr 7.
    Department of Human Neuroscience, Sapienza University of Rome, via dei Sabelli 108, 00185 Rome, Italy. Electronic address:
    Untreated phenylketonuria (PKU) results in severe neurodevelopmental disorders, which can be partially prevented by an early and rigorous limitation of phenylalanine (Phe) intake. Enzyme substitution therapy with recombinant Anabaena variabilis Phe Ammonia Lyase (rAvPAL) proved to be effective in reducing blood Phe levels in preclinical and clinical studies of adults with PKU. Aims of present study were: a) to gather proofs of clinical efficacy of rAvPAL treatment in preventing neurological impairment in an early treated murine model of PKU; b) to test the advantages of an alternative delivering system for rAvPAL such as autologous erythrocytes. Read More

    Functional Characterization of Novel Phenylalanine Hydroxylase p.Gln226Lys Mutation Revealed Its Non-responsiveness to Tetrahydrobiopterin Treatment in Hepatoma Cellular Model.
    Biochem Genet 2018 Apr 13. Epub 2018 Apr 13.
    Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, Belgrade, 11010, Serbia.
    Treatment with tetrahydrobiopterin (BH4) is the latest therapeutic option approved for patients with phenylketonuria (PKU)-one of the most frequent inborn metabolic diseases. PKU or phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene. Given that some PAH mutations are responsive to BH4 treatment while others are non-responsive, for every novel mutation that is discovered it is essential to confirm its pathogenic effect and to assess its responsiveness to a BH4 treatment in vitro, before the drug is administered to patients. Read More

    Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM).
    Mol Genet Metab 2018 Mar 31. Epub 2018 Mar 31.
    Department of Pediatrics, Division of Medical Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address:
    Background: Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) deficiency that results in phenylalanine (Phe) accumulation. Pegvaliase, PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL), converts Phe to trans-cinnamic acid and ammonia, and is a potential enzyme substitution therapy to lower blood Phe in adults with PKU.

    Methods: Two Phase 3 studies, PRISM-1 and PRISM-2, evaluated the efficacy and safety of pegvaliase treatment using an induction, titration, and maintenance dosing regimen in adults with PKU. Read More

    Three novel variants (p.Glu178Lys, p.Val245Met, p.Ser250Phe) of the phenylalanine hydroxylase (PAH) gene impair protein expression and function in vitro.
    Gene 2018 Apr 10. Epub 2018 Apr 10.
    Genetic and Prenatal Diagnostic Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:
    Phenylketonuria (PKU) is the most common inherited metabolic disease, an autosomal recessive disorder affecting >10,000 newborns each year globally. It can be caused by over 1000 different naturally occurring mutations in the phenylalanine hydroxylase (PAH) gene. We analyzed three novel naturally occurring PAH gene variants: p. Read More

    Psychological wellbeing in parents of children with phenylketonuria and association with treatment adherence.
    Minerva Pediatr 2018 Apr 12. Epub 2018 Apr 12.
    Clinical Psychology, Department of Health Sciences, University of Milan, Milan, Italy.
    Background: Phenylketonuria (PKU) is a rare metabolic disorder that leads to severe neurological abnormalities unless early treated with a strict phenylalanine (Phe)-restricted diet. The parents' involvement in PKU management is crucial and could lead to psychological distress; however, few studies have explored the parents' psychological wellbeing. The study aimed to: 1) evaluate the presence of psychological distress and impaired quality of life among parents of children with PKU, assessing the load of the diagnosis and the load of the treatment management; 2) explore the associations with their children's blood-Phe levels. Read More

    The S-oxidation (Referee 1 minor comment 1) of S-carboxymethyl-L-cysteine in hepatic cytosolic fractions from BTBR and Phenylketonuria enu1 and enu2 mice (Referee 1minor comment 2).
    Xenobiotica 2018 Apr 12:1-35. Epub 2018 Apr 12.
    b Imperial College London, Computational and Systems Medicine, Faculty of Medicine , South Kensington , London SW7 2AZ , UK.
    1. Mice that were heterozygous dominant for the enu1 and enu2 mutation in PAH resulted in hepatic PAH assays for SCMC that had significantly increased calculated K (wt/enu1, 1.84-2. Read More

    Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial.
    Mol Genet Metab 2018 Mar 18. Epub 2018 Mar 18.
    Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh and Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address:
    Introduction: Pegvaliase is a recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL) enzyme under investigation for treatment of adult phenylketonuria (PKU). This manuscript describes results of a randomized discontinuation trial (RDT) designed to evaluate the effects of pegvaliase treatment on blood phenylalanine (Phe) and neuropsychiatric outcomes in adults with PKU.

    Methods: PRISM-2 is a 4-part, Phase 3 study that enrolled adults with PKU receiving pegvaliase treatment (initiated in a prior Phase 2 or Phase 3 study). Read More

    Tryptophan metabolism: utility of plasmatic assay in phenylketonuria, a study in 6 adult patients.
    Ann Biol Clin (Paris) 2018 Apr;76(2):150-156
    Laboratoire des maladies héréditaires du métabolisme, Service de biochimie, biologie moléculaire, toxicologie environnementale, CHU de Grenoble-Alpes site Nord - Institut de biologie et de pathologie, La Tronche, France.
    Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive inborn error of metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH; EC 1.14.16. Read More

    A novel compound-primed multiplex ARMS-PCR (CPMAP) for simultaneous detection of common PAH gene mutations.
    Metab Brain Dis 2018 Apr 3. Epub 2018 Apr 3.
    Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, IR, Iran.
    In this study, we introduce a novel compound-primed multiplex ARMS PCR (CPMAP) for simultaneous detection of common PAH gene mutations. This approach was used successfully for simultaneous identification of six most common PAH gene mutations in 137 phenylketonuria patients in the Iranian population. A total of six normal and six mutant allele-specific primers and 4 common primers containing a tag sequence of 12 base pair at the 5'-end were designed and used in two separate optimized multiplex ARMS reactions followed by hot-start PCR. Read More

    Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria.
    Front Neurosci 2018 16;12:154. Epub 2018 Mar 16.
    Daniel Bovet Department of Psychology, Neurobiology Research Center, Sapienza Università di Roma, Rome, Italy.
    We studied group-I metabotropic glutamate (mGlu) receptors in Pah (ENU2) mice, which mimic the genetics and neurobiology of human phenylketonuria (PKU), a metabolic disorder characterized, if untreated, by autism, and intellectual disability (ID). Male ENU2 mice showed increased mGlu5 receptor protein levels in the hippocampus and corpus striatum (but not in the prefrontal cortex) whereas the transcript of the mGlu5 receptor was unchanged. No changes in mGlu1 receptor mRNA and protein levels were found in any of the three brain regions of ENU2 mice. Read More

    Disruption of PTPS Gene Causing Pale Body Color and Lethal Phenotype in the Silkworm, Bombyx mori.
    Int J Mol Sci 2018 Mar 29;19(4). Epub 2018 Mar 29.
    State Key Laboratory of Silkworm Genome Biology, Key Laboratory of Sericulture Biology and Genetic Breeding, Agricultural Ministry, College of Biotechnology, Southwest University, Chongqing 400715, China.
    Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the phenylalanine hydroxylase () gene or by defects in the tetrahydrobiopterin (BH4) synthesis pathway. Here, by positional cloning, we report that the 6-pyruvoyl-tetrahydropterin synthase () gene, encoding a key enzyme of BH4 biosynthesis, is responsible for the (albino C) mutation that displays pale body color, head shaking, and eventually lethality after the first molting in silkworm. Compared to wild type, the mutant produced more substrates (phenylalanine (Phe) and tyrosine (Tyr)) and generated less DOPA and dopamine. Read More

    Clinical and electrophysiological findings in patients with phenylketonuria and epilepsy: Reflex features.
    Epilepsy Behav 2018 Mar 23;82:46-51. Epub 2018 Mar 23.
    Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
    Objective: Phenylketonuria (PKU) is the most common form of amino acid metabolism disorders with autosomal recessive inheritance. The brain damage can be prevented by early diagnosis and a phenylalanine-restricted diet. Untreated or late-treated patients may show mental retardation and other cognitive dysfunctions, as well as motor disability and/or epilepsy. Read More

    Genotypes of patients with phenylalanine hydroxylase deficiency in the Wisconsin Amish.
    Mol Genet Metab Rep 2018 Jun 8;15:75-77. Epub 2018 Mar 8.
    University of Wisconsin Department of Pediatrics, Waisman Center Madison, WI, USA.
    In the Plain Community, there is an increased frequency of genetic disorders including phenylalanine hydroxylase (PAH) deficiency. Common pathogenic variants have been observed due to founder effect and closed community. This study obtained genotypes of 12 Plain individuals with PAH deficiency, identified through newborn screen or diagnosed by symptomatic presentation, who are receiving medical care at the University of Wisconsin metabolic clinic. Read More

    Secondary BH4 Deficiency Links Protein Homeostasis to Regulation of Phenylalanine Metabolism.
    Hum Mol Genet 2018 Mar 5. Epub 2018 Mar 5.
    University Children's Research@Kinder-UKE, University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Metabolic control of phenylalanine concentrations in body fluids is essential for cognitive development and executive function. The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH4). Physiologically, phenylalanine availability is governed by nutrient intake, whereas liver BH4 is kept at constant level. Read More

    Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels.
    J Nutr Metab 2018 8;2018:6352919. Epub 2018 Jan 8.
    Department of Clinical Genetics, Applied Human Molecular Genetics, Kennedy Center, Rigshospitalet, Denmark.
    Introduction: Management of phenylketonuria (PKU) is achieved through low-phenylalanine (Phe) diet, supplemented with low-protein food and mixture of free-synthetic (FS) amino acid (AA). Casein glycomacropeptide (CGMP) is a natural peptide released in whey during cheese-making and does not contain Phe. Lacprodan® CGMP-20 used in this study contained a small amount of Phe due to minor presence of other proteins/peptides. Read More

    Phenylketonuric diet negatively impacts on butyrate production.
    Nutr Metab Cardiovasc Dis 2018 Apr 31;28(4):385-392. Epub 2018 Jan 31.
    Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
    Background And Aims: Phenylalanine (Phe) restricted diet, combined with Phe-free l-amino acid supplementation, is the mainstay of treatment for phenylketonuria (PKU). Being the diet a key factor modulating gut microbiota composition, the aim of the present paper was to compare dietary intakes, gut microbiota biodiversity and short chain fatty acids (SCFAs) production in children with PKU, on low-Phe diet, and in children with mild hyperphenylalaninemia (MHP), on unrestricted diet.

    Methods And Results: We enrolled 21 PKU and 21 MHP children matched for gender, age and body mass index z-score. Read More

    Inborn Errors of Metabolism with Cognitive Impairment: Metabolism Defects of Phenylalanine, Homocysteine and Methionine, Purine and Pyrimidine, and Creatine.
    Pediatr Clin North Am 2018 Apr;65(2):267-277
    Division of Medical Genetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address:
    Phenylketonuria is a defect in phenylalanine metabolism resulting in the excretion of phenylketones and severe intellectual disability. The principle of eliminating the offending amino acid from the diet as a successful treatment strategy was demonstrated. The development of a low methionine diet to treat homocystinuria was established after identifying the transsulfuration pathway resulting in cysteine synthesis. Read More

    From a Single Child to Uniform Newborn Screening: My Lucky Life in Pediatric Medical Genetics.
    Annu Rev Genomics Hum Genet 2018 Mar 1. Epub 2018 Mar 1.
    Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA; email:
    Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by genetic disorders that could be treated if diagnosed in infancy, launched my six-decade career. This autobiographical article reflects on my childhood, early research, and professional experiences in pediatric genetics. My laboratory research focused on inborn errors of metabolism, including the glycogen storage diseases. Read More

    Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria.
    J Nutr 2018 Feb;148(2):194-201
    Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
    Background: Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (MFs).

    Objective: To assess lipid metabolism in participants with PKU consuming amino acid MFs (AA-MFs) or glycomacropeptide MFs (GMP-MFs), we conducted fatty acid and metabolomics analyses. Read More

    Language processing and executive functions in early treated adults with phenylketonuria (PKU).
    Cogn Neuropsychol 2018 Feb 28:1-23. Epub 2018 Feb 28.
    a School of Life and Health Sciences , Aston University , Birmingham , UK.
    We provide an in-depth analysis of language functions in early-treated adults with phenylketonuria (AwPKUs, N = 15-33), as compared to age- and education-matched controls (N = 24-32; N varying across tasks), through: a. narrative production (the Cinderella story), b. language pragmatics comprehension (humour, metaphors, inferred meaning), c. Read More

    Normal Growth in PKU Patients Under Low-Protein Diet in a Single-Center Cross-Sectional Study.
    JIMD Rep 2018 Feb 25. Epub 2018 Feb 25.
    Division of Metabolism, and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
    Dietary phenylalanine restriction in phenylketonuria (PKU) patients is usually mandatory in order to prevent cognitive impairment. The influence of a low-protein diet on growth has raised concerns in families and caregivers. This paper aims to investigate the growth in PKU patients treated with a low-protein diet including supplementation of amino acids and other nutrients according to standard protocols. Read More

    Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations.
    Pigment Cell Melanoma Res 2018 Feb 23. Epub 2018 Feb 23.
    Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
    Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Read More

    Parenting a Child with Phenylketonuria (PKU): an Interpretative Phenomenological Analysis (IPA) of the Experience of Parents.
    J Genet Couns 2018 Feb 21. Epub 2018 Feb 21.
    Division of Psychology and Mental Health, University of Manchester, Manchester, UK.
    Phenylketonuria (PKU) is a rare inherited metabolic disorder which can cause neurological damage if left untreated. PKU is identified through newborn screening in developed countries, and treatment begins immediately to prevent these severe consequences. When a child is diagnosed, parents must assume immediate responsibility for the management of PKU and prevention of neurological damage. Read More

    Subacute onset leukodystrophy and visual-spatial disorders revealing phenylketonuria combined with homocysteinmia in adulthood: A case report.
    Medicine (Baltimore) 2018 Feb;97(8):e9801
    Department of Neurology, The Second People's Hospital of Guiyang, Guiyang, Guizhou, China.
    Rationale: Phenylketonuria (PKU) is a metabolic disorder, which manifests a progressive irreversible neurological impairment during infancy and childhood. Hyperhomocysteinemia also showed that it might be involved in pathophysiology of many neuropsychiatric disorders. The late-onset clinical manifestations of these 2 diseases have not been reported elsewhere. Read More

    Metabolomic Insights into the Nutritional Status of Adults and Adolescents with Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid and Glycomacropeptide Medical Foods.
    J Nutr Metab 2017 31;2017:6859820. Epub 2017 Dec 31.
    Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
    Background: Nutrient status in phenylketonuria (PKU) requires surveillance due to the restrictive low-Phe diet in combination with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF). Micronutrient profiles of medical foods are diverse, and optimal micronutrient supplementation in PKU has not been established.

    Methods: In a crossover design, 30 participants with PKU were randomized to consume AA-MF and Glytactin™ GMP-MF in combination with a low-Phe diet for 3 weeks each. Read More

    Brain bioenergetics in rats with acute hyperphenylalaninemia.
    Neurochem Int 2018 Feb 14. Epub 2018 Feb 14.
    Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. Electronic address:
    Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism caused by deficient phenylalanine hydroxylase (PAH) activity. The deficiency results in increased levels of Phe and its metabolites in fluids and tissues of patients. PKU patients present neurological signs and symptoms including hypomyelination and intellectual deficit. Read More

    Multiple SNPs Detection Based on Lateral Flow Assay for Phenylketonuria Diagnostic.
    Anal Chem 2018 Mar 16;90(5):3430-3436. Epub 2018 Feb 16.
    McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences , Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100005 , China.
    Single nucleotide polymorphisms (SNPs) are closely related to genetic diseases, but current SNP detection methods, such as DNA microarrays that include tedious procedures and expensive, sophisticated instruments, are unable to perform rapid SNPs detection in clinical practice, especially for those multiple SNPs related to genetic diseases. In this study, we report a sensitive, low cost, and easy-to-use point-of-care testing (POCT) system formed by combining amplification refractory mutation system (ARMS) polymerase chain reaction with gold magnetic nanoparticles (GMNPs) and lateral flow assay (LFA) noted as the ARMS-LFA system, which allow us to use a uniform condition for multiple SNPs detection simultaneously. The genotyping results can be explained by a magnetic reader automatically or through visual interpretation according to the captured GMNPs probes on the test and control lines of the LFA device. Read More

    Supplementation of Micronutrient Selenium in Metabolic Diseases: Its Role as an Antioxidant.
    Oxid Med Cell Longev 2017 26;2017:7478523. Epub 2017 Dec 26.
    School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
    Selenium is an essential mineral naturally found in soil, water, and some of the food. As an antioxidant, it is one of the necessary trace elements in human body and has been suggested as a dietary supplement for health benefit. Although the human body only needs a trace amount of selenium every day, plenty of recent studies have revealed that selenium is indispensable for maintaining normal functions of metabolism. Read More

    Assessing the Phenylketonuria Screening Program in Newborns, Iran 2015-2016.
    Acta Med Iran 2018 Jan;56(1):49-55
    Social Determinants of Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. AND Department of Community Health, Shahrekord University of Medical Sciences, Shahrekord, Iran.
    Phenylketonuria is one of the most important congenital disorders and an autosomal recessive metabolic disease that can cause irreversible brain damages, mental retardation, and cognitive disorders if left untreated. In order to reduce the genetic abnormalities caused by this metabolic disease, screening programs are implemented. The quality of the program must be properly assessed to achieve the objectives of this program if promoting children's health is of concern. Read More

    Vitamin/mineral and micronutrient status in patients with classical phenylketonuria.
    Clin Nutr 2018 Feb 9. Epub 2018 Feb 9.
    Dokuz Eylul University, Division of Pediatric Metabolism and Nutrition, Izmir, Turkey. Electronic address:
    Background & Aims: Strict low-phenylalanine diet is associated with an increased risk of developing micronutrient deficiencies in patients with phenylketonuria (PKU). The primary objective of this single-center, case-control study was to assess the nutritional parameters of patients with PKU on strict low-phenylalanine diet without vitamin and mineral supplementation compared to a healthy control group. Secondary objective was to identify the adequacy of vitamin/mineral supplementation in phenylalanine-free (Phe-free) amino acid formulas. Read More

    Developmental Trajectories of Executive and Verbal Processes in Children with Phenylketonuria.
    Dev Neuropsychol 2018 12;43(3):207-218. Epub 2018 Feb 12.
    a Department of Psychological & Brain Sciences , Washington University , St. Louis , Missouri , United States of America.
    Phenylketonuria (PKU) is a hereditary disorder characterized by disrupted phenylalanine metabolism and cognitive impairment. However, the precise nature and developmental trajectory of this cognitive impairment remains unclear. The present study used a verbal fluency task to dissociate executive and verbal processes in children with PKU (n = 23; 7-18 years) and controls (n = 44; 7-19 years). Read More

    PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population.
    Kaohsiung J Med Sci 2018 Feb 5;34(2):89-94. Epub 2017 Oct 5.
    Department of Medical Laboratory, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, China. Electronic address:
    Phenylketonuria (PKU) is a common autosomal recessive disorder of phenylalanine metabolism and mainly results a deficiency of phenylalanine hydroxylase gene (PAH). The incidence of various PAH mutations have race and ethnicity differences. We report a spectrum of PAH mutations complied from 35 PKU children who are all Chinese Han population from north Jiangsu in this study. Read More

    Mutational spectrum of the phenylalanine hydroxylase gene in patients with phenylketonuria in the central region of China.
    Scand J Clin Lab Invest 2018 May 1;78(3):211-218. Epub 2018 Feb 1.
    a The Third Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
    Phenylketonuria (PKU, OMIM 261600) caused by phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disease that is characterized by abnormalities of phenylalanine metabolism. In this study, a total of 77 patients, originating from the central region of China and who were diagnosed with PAH deficiency at the third affiliated hospital of Zhengzhou University, were enrolled in this study. The 13 exons and 12 flanking introns of the PAH gene were analyzed by Sanger sequencing and next generation sequencing. Read More

    Arterial stiffness assessment in patients with phenylketonuria.
    Medicine (Baltimore) 2017 Dec;96(51):e9322
    Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Service of Neonatology, Department of Pediatrics, Hospital Clínico Universitario de Santiago, CIBERER, Health Research Institute of Santiago de Compostela (IDIS), A Choupana.
    In patients with phenylketonuria (PKU) compliant to diet greater tendency to overweight and higher inflammatory biomarkers levels than controls were reported. Although this could lead to atherogenesis, the elastic properties of large arteries in PKU patients have never been assessed. The aim of this study was to assess arterial stiffness measured by applanation tonometry in PKU patients compared to healthy controls. Read More

    The role of the clinician in the multi-omics era: are you ready?
    J Inherit Metab Dis 2018 Jan 23. Epub 2018 Jan 23.
    Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
    Since Garrod's first description of alkaptonuria in 1902, and newborn screening for phenylketonuria introduced in the 1960s, P4 medicine (preventive, predictive, personalized, and participatory) has been a reality for the clinician serving patients with inherited metabolic diseases. The era of high-throughput technologies promises to accelerate its scale dramatically. Genomics, transcriptomics, epigenomics, proteomics, glycomics, metabolomics, and lipidomics offer an amazing opportunity for holistic investigation and contextual pathophysiologic understanding of inherited metabolic diseases for precise diagnosis and tailored treatment. Read More

    Non-invasive prenatal testing of pregnancies at risk for phenylketonuria.
    Arch Dis Child Fetal Neonatal Ed 2018 Jan 20. Epub 2018 Jan 20.
    Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
    Background: Phenylketonuria (PKU) is a common metabolic disorder caused predominately by mutations in the phenylalanine hydroxylase () gene. The aim of the study was to design and validate the performance of a non-invasive prenatal test (NIPT) for PKU using circulating single molecule amplification and resequencing technology (cSMART).

    Methods: A total of 18 couples at genetic risk for having a child with PKU were recruited to the study. Read More

    The tyranny of the averages and the indiscriminate use of risk factors in public health: The case of coronary heart disease.
    SSM Popul Health 2017 Dec 18;3:684-698. Epub 2017 Aug 18.
    Unit for Cardiovascular Epidemiology, CRC, Faculty of Medicine, Lund University, Sweden.
    Modern medicine is overwhelmed by a plethora of both established risk factors and novel biomarkers for diseases. The majority of this information is expressed by probabilistic measures of association such as the odds ratio (OR) obtained by calculating differences in average "risk" between exposed and unexposed groups. However, recent research demonstrates that even ORs of considerable magnitude are insufficient for assessing the ability of risk factors or biomarkers to distinguish the individuals who will develop the disease from those who will not. Read More

    Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice.
    Mol Genet Metab 2018 Jan 19;123(1):6-20. Epub 2017 Oct 19.
    Department of Medical and Molecular Genetics, Oregon Health & Science University, Mailstop L-103, 3181 Sam Jackson Park Rd., Portland, OR 97239, USA. Electronic address:
    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pah mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice. Read More

    Blood phenylalanine instability strongly correlates with anxiety in phenylketonuria.
    Mol Genet Metab Rep 2018 Mar 27;14:80-82. Epub 2017 Dec 27.
    Department of Medical Genetics, Jagiellonian University Medical College, Krakow, Poland.
    We assessed the relationship between anxiety and long-term metabolic control in adolescents with phenylketonuria (PKU). We used a standardized psychological test to measure anxiety level and analyzed lifelong blood phenylalanine stability in a selected group of 25 PKU teenagers with treatment adherence problems. We demonstrated significant correlations of anxiety with variability of blood phenylalanine concentrations and with severity of hyperphenylalaninemia. Read More

    Flux analysis of inborn errors of metabolism.
    J Inherit Metab Dis 2018 Jan 9. Epub 2018 Jan 9.
    Section of Systems Medicine and Metabolic Signaling, Laboratory of Pediatrics, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
    Patients with an inborn error of metabolism (IEM) are deficient of an enzyme involved in metabolism, and as a consequence metabolism reprograms itself to reach a new steady state. This new steady state underlies the clinical phenotype associated with the deficiency. Hence, we need to know the flux of metabolites through the different metabolic pathways in this new steady state of the reprogrammed metabolism. Read More

    Correction to: Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.
    BMC Med Genet 2018 Jan 9;19(1). Epub 2018 Jan 9.
    Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Jianshe Rd, Erqi District, Zhengzhou, Henan, 450052, People's Republic of China.
    Following publication of the original article [1], the authors reported an error in Table 3 on page 4. Variant No. 18 should be " p. Read More

    [Singleton and twin pregnancies of PKU patients - individual variability of phenylalanine tolerance: experience of a single treatment center (Preliminary report)].
    Dev Period Med 2017 ;21(4):344-360
    Klinika Pediatrii, Instytut Matki i Dziecka, Warszawa, Polska, Przykliniczna Poradnia Fenyloketonurii, Instytut Matki i Dziecka, Warszawa, Polska.
    Phenylketonuria (PKU) is the autosomal recessive deficiency of phenylalanine hydroxylase resulting in the accumulation of phenylalanine (Phe) in blood and in the brain. Phe restriction in a patient's diet is determined depending on the amount of Phe intake which allows for stable blood Phe levels within the therapeutic range of 120-360µmol/L. In clinical practice the empirical determination of Phe tolerance relies on frequent assessment of blood Phe concentrations in relation to Phe intake from food records. Read More

    Characterization of Phenyalanine Hydroxylase Gene Mutations in Chilean PKU Patients.
    JIMD Rep 2017 Dec 30. Epub 2017 Dec 30.
    Instituto de Nutrición y Tecnología de los Alimentos, Dr. Fernando Monckeberg Barros, Universidad de Chile, Santiago, Chile.
    Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive disease, caused by mutations in the Phenylalanine Hydroxylase (PAH) gene situated in chromosome 12q22-q24.2. This gene has 13 exons. Read More

    Effect of Blood Phenylalanine Levels on Oxidative Stress in Classical Phenylketonuric Patients.
    Cell Mol Neurobiol 2017 Dec 28. Epub 2017 Dec 28.
    Division of Physiology, Harran University, Sanlıurfa, Turkey.
    Mental retardation, which occurs in phenylketonuric patients, is associated with increased levels of phenylalanine, increased oxidative stress, and an imbalance of amino acids in the brain. Recent studies have shown that oxidative stress plays a role in the pathogenesis of phenylketonuria. In this work, we aimed to compare the influence of blood phenylalanine levels on oxidative stress parameters in phenylketonuric patients who divided patients into groups according to blood Phe levels during follow-up visits and compared these groups with healthy controls. Read More

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