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    Modulating the pH Activity Profiles of Phenylalanine Ammonia Lyase from Anabaena variabilis by Modification of Center-Near Surface Residues.
    Appl Biochem Biotechnol 2017 Mar 25. Epub 2017 Mar 25.
    Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China.
    Phenylalanine ammonia lyase from Anabaena variabilis (Av-PAL) is a candidate for the treatment of phenylketonuria (PKU). However, Av-PAL shows its optimal pH at 8.5 and maintains only 70% of its highest activity when pH decreases to 7. Read More

    Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria.
    Ann Nutr Metab 2017 Mar 24;70(2):111-121. Epub 2017 Mar 24.
    Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
    Introduction: In phenylketonuria (PKU), a natural protein-restricted dietary treatment prevents severe cognitive impairment. Nutrient deficiencies may occur due to strict diet. This study is aimed at evaluating the dietary intake and blood concentrations of micronutrients and essential fatty acids (FA), bone mineral density (BMD) and fracture history in patients on long-term dietary treatment. Read More

    Impact of phenylketonuria type meal on appetite, thermic effect of feeding and postprandial fat oxidation.
    Clin Nutr 2017 Mar 8. Epub 2017 Mar 8.
    School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address:
    Background: Dietary management of phenylketonuria (PKU) requires the replacement of natural protein-containing foods with special low protein foods. The effect of a PKU type diet on factors contributing to energy balance requires investigation.

    Objective: To investigate the impact of a PKU type meal on appetite ratings, gut appetite hormones, thermic effect of feeding (TEF) and fat oxidation. Read More

    Cognitive Profile and Mental Health in Adult Phenylketonuria: A PKU-COBESO Study.
    Neuropsychology 2017 Mar 20. Epub 2017 Mar 20.
    Objective: Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive functions compared to healthy controls. Cognitive problems in phenylketonuria have often been associated with phenylalanine levels. The present study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment. Read More

    Effects of Short-Term Calcium Supplementation in Children and Adolescents with Phenylketonuria.
    J Clin Densitom 2017 Mar 13. Epub 2017 Mar 13.
    Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
    Reduction of bone mineral density and the risk of osteopenia have been reported to occur in phenylketonuria (PKU) patients. This study aimed to evaluate the short-term effects of calcium supplementation in phenylketonuric children and adolescents. The study included 18 patients with PKU aged 5-18 yr (61% male) under clinical and nutritional treatment. Read More

    Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.
    JIMD Rep 2017 Mar 15. Epub 2017 Mar 15.
    Service de médecine interne, CHRU de Tours, Tours, France.
    Background: Several studies have highlighted disturbance of redox homeostasis in patients with phenylketonuria (PKU) which may be associated with neurological disorders observed in patients, especially during adulthood when phenylalanine restrictive diets are not maintained. The aim of this study was to assess the antioxidant profile in a cohort of PKU patients in comparison to the controls and to evaluate its relation to biochemical parameters especially phenylalaninemia.

    Methods: We measured RNA expression of 22 antioxidant genes and reactive oxygen species (ROS) levels in white blood cells of 10 PKU patients and 10 age- and gender-matched controls. Read More

    Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study.
    Mol Genet Metab 2017 Mar 6. Epub 2017 Mar 6.
    Department of Psychiatry, Drexel University, College of Medicine, Philadelphia, PA, USA; Department of Pediatrics, Drexel University, College of Medicine, Philadelphia, PA, USA.
    Adults with phenylketonuria (PKU) may experience neurologic and psychiatric disorders, including intellectual disability, anxiety, depression, and neurocognitive dysfunction. Identifying the prevalence and prevalence ratios of these conditions will inform clinical treatment. This nested, case-controlled study used International Classification of Diseases, Ninth Revision (ICD-9) codes from the MarketScan® insurance claims databases from 2006 to 2012 and healthcare claims data for US-based employer and government-sponsored health plans. Read More

    Impaired Neurotransmission in Early-treated Phenylketonuria Patients.
    Semin Pediatr Neurol 2016 Nov 9;23(4):332-340. Epub 2016 Nov 9.
    From the *Department of Neurology, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Madrid, Spain.
    Cerebral neurotransmitter (NT) deficiency has been suggested as a contributing factor in the pathophysiology of brain dysfunction in phenylketonuria (PKU), even in early-treated phenylketonuric patients. The study aimed to review dopamine and serotonin status in PKU, and the effect of the impaired neurotransmission. Several mechanisms are involved in the pathophysiology of PKU, primarily characterized by impaired dopamine and serotonin synthesis. Read More

    Neonatal Screening for Inherited Metabolic Diseases in 2016.
    Semin Pediatr Neurol 2016 Nov 16;23(4):257-272. Epub 2016 Nov 16.
    From the Seccción de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica y Genética Molecular, Hospital ClinicHospital Clínic, CIBERER, IDIBAPS, Barcelona, Spain. Electronic address:
    The scope of newborn screening (NBS) programs is continuously expanding. NBS programs are secondary prevention interventions widely recognized internationally in the "field of Public Health." These interventions are aimed at early detection of asymptomatic children affected by certain diseases, with the objective to establish a definitive diagnosis and apply the proper treatment to prevent further complications and sequelae and ensure a better quality of life. Read More

    Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria.
    PLoS One 2017 10;12(3):e0173269. Epub 2017 Mar 10.
    BioMarin Pharmaceutical, Novato, California, United States of America.
    Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. Read More

    Development of the US English version of the phenylketonuria - quality of life (PKU-QOL) questionnaire.
    Health Qual Life Outcomes 2017 Mar 9;15(1):46. Epub 2017 Mar 9.
    Mapi Research Trust, 27 rue de la Villette, Lyon, 69003, France.
    Background: Phenylketonuria (PKU) is a rare genetic disorder caused by a defect in the metabolism of phenylalanine (PHE) resulting in elevated blood and brain PHE levels, and leading to cognitive, emotional, and psychosocial problems. The phenylketonuria - quality of life (PKU-QOL) questionnaire was the first self-administered disease-specific instrument developed to assess the impact of PKU and its treatment on the health-related quality of life (HRQL) of patients and their caregivers. Available in four versions (child, adolescent, adult and parent), the PKU-QOL was simultaneously developed and validated in seven countries [i. Read More

    Pretreatment cognitive and neural differences between sapropterin dihydrochloride responders and non-responders with phenylketonuria.
    Mol Genet Metab Rep 2017 Sep 23;12:8-13. Epub 2017 Feb 23.
    Department of Psychological and Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO 63130, USA; Department of Pediatrics, Campus Box 8116, Washington University School of Medicine, St. Louis, MO 63110, USA.
    Sapropterin dihydrochloride (BH4) reduces phenylalanine (Phe) levels and improves white matter integrity in a subset of individuals with phenylketonuria (PKU) known as "responders." Although prior research has identified biochemical and genotypic differences between BH4 responders and non-responders, cognitive and neural differences remain largely unexplored. To this end, we compared intelligence and white matter integrity prior to treatment with BH4 in 13 subsequent BH4 responders with PKU, 16 subsequent BH4 non-responders with PKU, and 12 healthy controls. Read More

    The impact of phenylalanine levels on cognitive outcomes in adults with phenylketonuria: Effects across tasks and developmental stages.
    Neuropsychology 2017 Mar;31(3):242-254
    Queen Elizabeth Hospital.
    Objective: Phenylketonuria (PKU) is due to an inability to metabolize the amino acid phenylalanine (Phe), leading to its accumulation in the brain. Phe levels can be controlled following a protein-free diet, but cognitive impairments are still present. A number of questions remain to be answered related to which type of metabolic control is important, the age when it is important, the cognitive functions which are most affected and, the best tests to use to monitor cognitive health. Read More

    Sapropterin treatment does not enhance the health-related quality of life of patients with phenylketonuria and their parents.
    Acta Paediatr 2017 Feb 24. Epub 2017 Feb 24.
    Department of General Pediatrics, Münster University Children's Hospital, Münster, Germany.
    Aim: Sapropterin causes reductions in blood phenylalanine concentrations in sensitive patients with phenylketonuria (PKU). We examined whether the subsequent relaxation of dietary restrictions influenced the quality of life (QoL) of patients and parents.

    Methods: The study cohort comprised 112 patients with PKU followed at the metabolic centre at Münster University Children's Hospital, Germany, from 2012 to 2015. Read More

    Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals.
    Mol Genet Metab Rep 2017 Mar 3;10:92-95. Epub 2017 Feb 3.
    Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, CSUR de Errores Congénitos del Metabolismo, Madrid, Spain.
    Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. Read More

    Risk Factors for Birth Defects.
    Obstet Gynecol Surv 2017 Feb;72(2):123-135
    Professor, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC.
    Importance: Major congenital abnormalities, or birth defects, carry significant medical, surgical, cosmetic, or lifestyle consequences. Such abnormalities may be syndromic, involving multiple organ systems, or can be isolated. Overall, 2% to 4% of live births involve congenital abnormalities. Read More

    Mutation Analysis in Classical Phenylketonuria Patients Followed by Detecting Haplotypes Linked to Some PAH Mutations.
    Clin Lab 2017 Feb;63(2):295-300
    Background: Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). The gold standard for confirming PKU and PAH deficiency is detecting causal mutations by direct sequencing of the coding exons and splicing involved sequences of the PAH gene. Furthermore, haplotype analysis could be considered as an auxiliary approach for detecting PKU causative mutations before direct sequencing of the PAH gene by making comparisons between prior detected mutation linked-haplotypes and new PKU case haplotypes with undetermined mutations. Read More

    Subtle visuomotor deficits and reduced benefit from practice in early treated phenylketonuria.
    J Clin Exp Neuropsychol 2017 Feb 6:1-10. Epub 2017 Feb 6.
    a Experimental Psychology & Brain Disorders Laboratory , Fundació Sant Joan de Déu, Hospital Sant Joan de Déu , Esplugues de Llobregat, Barcelona , Spain.
    Introduction: Phenylketonuria (PKU) is a rare metabolic disease that causes slight-to-severe neurological symptoms. Slow performance has been observed in PKU but the influence of high-order (i.e. Read More

    Adherence to clinic recommendations among patients with phenylketonuria in the United States.
    Mol Genet Metab 2017 Mar 6;120(3):190-197. Epub 2017 Jan 6.
    Medical Affairs, BioMarin Pharmaceutical, Inc., Novato, CA, United States.
    Objective: Assess current management practices of phenylketonuria (PKU) clinics across the United States (US) based on the key treatment metrics of blood phenylalanine (Phe) concentrations and blood Phe testing frequency, as well as patient adherence to their clinic's management practice recommendations.

    Methods: An online survey was conducted with medical professionals from PKU clinics across the US from July to September 2015. Forty-four clinics participated in the survey and account for approximately half of PKU patients currently followed in clinics in the US (Berry et al. Read More

    Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability.
    Am J Hum Genet 2017 Feb 26;100(2):257-266. Epub 2017 Jan 26.
    UMR1141, PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris 75019, France; Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris 75019, France. Electronic address:
    Phenylketonuria (PKU, phenylalanine hydroxylase deficiency), an inborn error of metabolism, can be detected through newborn screening for hyperphenylalaninemia (HPA). Most individuals with HPA harbor mutations in the gene encoding phenylalanine hydroxylase (PAH), and a small proportion (2%) exhibit tetrahydrobiopterin (BH4) deficiency with additional neurotransmitter (dopamine and serotonin) deficiency. Here we report six individuals from four unrelated families with HPA who exhibited progressive neurodevelopmental delay, dystonia, and a unique profile of neurotransmitter deficiencies without mutations in PAH or BH4 metabolism disorder-related genes. Read More

    Investigation of Fibril Forming Mechanisms of l-Phenylalanine and l-Tyrosine: Microscopic Insight toward Phenylketonuria and Tyrosinemia Type II.
    J Phys Chem B 2017 Feb 8;121(7):1533-1543. Epub 2017 Feb 8.
    Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, WB, India.
    Phenylketonuria and tyrosinemia type II, the two metabolic disorders, are originated due to the complications in metabolism of phenylalanine (Phe) and tyrosine (Tyr), respectively. Several neurological injuries, involving microcephaly, mental retardation, epilepsy, motor disease, and skin problems etc., are the symptoms of these two diseases. Read More

    Construction of different calibration models by FTIR/ATR spectra and their application in screening of phenylketonuria.
    Spectrochim Acta A Mol Biomol Spectrosc 2017 Apr 10;177:33-40. Epub 2017 Jan 10.
    School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; The Key Unit of Chinese Medicine Digitalization Quality Evaluation of SATCM, Guangzhou 510006, PR China; The Research Center for Quality Engineering Technology of Traditional Chinese Medicine in Guangdong Universities, Guangzhou 510006, PR China.
    Objective: To construct different calibration models by using FTIR/ATR spectra and apply them for the screening of phenylketonuria for the newborns.

    Method: 69 dried blood spots samples were collected, of which the concentrations of phenylalanine (Phe) and tyrosine (Tyr) were determined by tandem mass spectrometry method. The FTIR/ATR method was used to collect the spectra of the samples. Read More

    Glycomacropeptide in children with phenylketonuria: does its phenylalanine content affect blood phenylalanine control?
    J Hum Nutr Diet 2017 Jan 22. Epub 2017 Jan 22.
    Birmingham Children's Hospital, Dietetic Department, Birmingham, UK.
    Background: In phenylketonuria (PKU), there are no data available for children with respect to evaluating casein glycomacropeptide (CGMP) as an alternative to phenylalanine-free protein substitutes [Phe-free L-amino acid (AA)]. CGMP contains a residual amount of phenylalanine, which may alter blood phenylalanine control.

    Methods: In a prospective 6-month pilot study, we investigated the effect on blood phenylalanine control of CGMP-amino acid (CGMP-AA) protein substitute in 22 PKU subjects (13 boys, nine girls), median age (range) 11 years (6-16 years). Read More

    Development of a new UPLC-ESI-MS/MS method for the determination of biopterin and neopterin in dried blood spot.
    Clin Chim Acta 2017 Mar 18;466:145-151. Epub 2017 Jan 18.
    Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. Electronic address:
    Background: (6R)-5,6,7,8-tetrahydrobiopterin (BH4) deficiencies are rare inherited defects of synthesis or regeneration of BH4. Due to the resulting hyperphenylalaninemia (HPA), some of them are detected by newborn screening and require the assessment of the pattern of neopterin (Neo) and biopterin (Bio) excretion in urine to be confirmed. Aim of present study was to develop a method for the measurement of these diagnostic biomarkers in dried blood spot (DBS). Read More

    Key European guidelines for the diagnosis and management of patients with phenylketonuria.
    Lancet Diabetes Endocrinol 2017 Jan 9. Epub 2017 Jan 9.
    Dietetic Department, Birmingham Children's Hospital, Birmingham, UK.
    We developed European guidelines to optimise phenylketonuria (PKU) care. To develop the guidelines, we did a literature search, critical appraisal, and evidence grading according to the Scottish Intercollegiate Guidelines Network method. We used the Delphi method when little or no evidence was available. Read More

    Dietary glycemic index, glycemic load and metabolic profile in children with phenylketonuria.
    Nutr Metab Cardiovasc Dis 2017 Feb 21;27(2):176-182. Epub 2016 Nov 21.
    Department of Pediatrics, San Paolo Hospital, Department of Health Science, University of Milan, Milan 20142, Italy. Electronic address:
    Background And Aims: No data exist in the current literature on the glycemic index (GI) and glycemic load (GL) of the diet of phenylketonuric (PKU) children. The aims of this study were to examine the dietary GI and GL in PKU children on a low-phenylalanine (Phe)-diet and to evaluate whether an association may exist between the carbohydrate quality and the metabolic profile.

    Methods: Twenty-one PKU children (age 5-11 years) and 21 healthy children, gender and age matched, were enrolled. Read More

    Cognitive outcomes in early-treated adults with phenylketonuria (PKU): A comprehensive picture across domains.
    Neuropsychology 2017 Mar 12;31(3):255-267. Epub 2017 Jan 12.
    School of Life and Health Sciences, Aston University.
    Objective: Phenylketonuria (PKU) is an inherited metabolic disease which affects cognitive functions due to an inability to metabolize phenylalanine which leads to the accumulation of toxic by-products (Phe) in the brain. PKU can be effectively treated with a low phenylalanine diet, but some cognitive deficits remain. Studies have reported impairments, especially for processing speed and executive functions, but there is a lack of comprehensive assessment across cognitive domains. Read More

    Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations.
    Acta Sci Pol Technol Aliment 2016 Apr-Jun;15(2):221-225
    Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poland.
    Background: High oxidative stress and a reduced potential for free radical scavenging in phenylketonuria (PKU) patients, a phenomenon confirmed in a few studies, may lead to systemic chronic inflammation. The aim of this study was to compare the inflammation status, as assessed by interleukin 6 and interleukin 8 concentrations, in patients with PKU and in healthy controls.

    Methods: Twenty patients with classical PKU, aged 18-34 years and under dietary control, were enrolled in the study. Read More

    The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background.
    Front Behav Neurosci 2016 20;10:233. Epub 2016 Dec 20.
    Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands.
    To unravel the role of gene mutations in the healthy and the diseased state, countless studies have tried to link genotype with phenotype. However, over the years, it became clear that the strain of mice can influence these results. Nevertheless, identical gene mutations in different strains are often still considered equals. Read More

    The Indicator Amino Acid Oxidation Method with the Use of l-[1-13C]Leucine Suggests a Higher than Currently Recommended Protein Requirement in Children with Phenylketonuria.
    J Nutr 2017 Feb 4;147(2):211-217. Epub 2017 Jan 4.
    Department of Pediatrics and
    Background: Phenylketonuria is characterized by mutations in the Phe hydroxylase gene that leads to the accumulation of Phe in plasma and the brain. The standard of care for phenylketonuria is nutritional management with dietary restriction of Phe and the provision of sufficient protein and energy for growth and health maintenance. The protein requirement in children with phenylketonuria is empirically determined based upon phenylketonuria nutritional guidelines that are adjusted individually in response to biochemical markers and growth. Read More

    Host conditioning and rejection monitoring in hepatocyte transplantation in humans.
    J Hepatol 2016 Dec 24. Epub 2016 Dec 24.
    Thomas E. Starzl Transplant Institute, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address:
    Background & Aims: Hepatocyte transplantation partially corrects genetic disorders and has been associated anecdotally with reversal of acute liver failure. Monitoring for graft function and rejection has been difficult, and has contributed to limited graft survival. Here we aimed to use preparative liver-directed radiation therapy, and continuous monitoring for possible rejection in an attempt to overcome these limitations. Read More

    Challenges of Implementation of the National Phenylketonuria Screening Program in Iran: A Qualitative Study.
    Electron Physician 2016 Oct 25;8(10):3048-3056. Epub 2016 Oct 25.
    Assistant Professor, Health Services Management, Health Management and Social Development Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
    Introduction: Newborn screening (NBS) is a public health measure aimed at identification of early cases, management of afflicted infants, and making efforts to reduce the morbidity and mortality among newborns. All countries may face challenges in implementation of screening programs. The present study aimed to determine the challenges of implementation of the National Phenylketonuria (PKU) Screening Program in Iran. Read More

    Biochemical Evaluation of Phenylalanine Ammonia Lyase from Endemic Plant Cyathobasis fruticulosa (Bunge) Aellen. for the Dietary Treatment of Phenylketonuria.
    Food Technol Biotechnol 2016 Sep;54(3):296-303
    Gazi University, Faculty of Science, Department of Biology, TR-06500 Teknikokullar, Ankara, Turkey.
    Enzyme substitution therapy with the phenylalanine ammonia lyase (PAL) is a new approach to the treatment of patients with phenylketonuria (PKU). This enzyme is responsible for the conversion of phenylalanine to trans-cinnamic acid. We assessed the PAL enzyme of the endemic plant Cyathobasis fruticulosa (Bunge) Aellen. Read More

    Late-diagnosed phenylketonuria in an eight-year-old boy with dyslexia and attention-deficit hyperactivity disorder.
    Turk J Pediatr 2016 ;58(1):94-96
    Pediatric Metabolic Diseases Unit, Department of Pediatrics, Hacettepe University Faculy of Medicine, Ankara, Turkey.
    Phenylketonuria, previously a common cause of severe intellectual disability, is a metabolic disorder now promptly diagnosed and effectively treated thanks to newborn screening programs. Here, we report a male patient presenting with dyslexia and attention-deficit hyperactivity disorder, who was diagnosed with mild phenylketonuria at eight years of age. Earlier recognition and treatment before the establishment of irreversible brain damage would have resulted in better neurobehavioural outcomes. Read More

    Post-Translational Incorporation of L-Phenylalanine into the C-Terminus of α-Tubulin as a Possible Cause of Neuronal Dysfunction.
    Sci Rep 2016 Dec 1;6:38140. Epub 2016 Dec 1.
    Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC-CONICET, and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, Córdoba, Argentina.
    α-Tubulin C-terminus undergoes post-translational, cyclic tyrosination/detyrosination, and L-Phenylalanine (Phe) can be incorporated in place of tyrosine. Using cultured mouse brain-derived cells and an antibody specific to Phe-tubulin, we showed that: (i) Phe incorporation into tubulin is reversible; (ii) such incorporation is not due to de novo synthesis; (iii) the proportion of modified tubulin is significant; (iv) Phe incorporation reduces cell proliferation without affecting cell viability; (v) the rate of neurite retraction declines as level of C-terminal Phe incorporation increases; (vi) this inhibitory effect of Phe on neurite retraction is blocked by the co-presence of tyrosine; (vii) microtubule dynamics is reduced when Phe-tubulin level in cells is high as a result of exogenous Phe addition and returns to normal values when Phe is removed; moreover, microtubule dynamics is also reduced when Phe-tubulin is expressed (plasmid transfection). It is known that Phe levels are greatly elevated in blood of phenylketonuria (PKU) patients. Read More

    Partial hydatidiform mole in a phenylketonuria patient treated with sapropterin dihydrochloride.
    Gynecol Endocrinol 2017 Jan 29;33(1):19-20. Epub 2016 Nov 29.
    a Division of Pediatric Metabolism , Department of Pediatrics, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
    Strict control of hyperphenylalaninemia is necessary in pregnant women with phenylketonuria (PKU) in order to prevent phenylalanine embryopathy in the fetus, characterized by intrauterine growth restriction, dysmorphic facies, congenital heart disease, microcephaly and intellectual disability, collectively known as maternal PKU syndrome. Sapropterin dihydrochloride (SD), an alternative or adjunct to dietary therapy in patients with tetrahydrobiopterin (BH4)-responsive PKU, has recently been used in several cases to treat PKU during pregnancy with satisfactory results. Here, we report two pregnancies treated with SD and unrestricted diet in a patient with BH4-responsive mild PKU. Read More

    Affinity chromatography matrices for depletion and purification of casein glycomacropeptide from bovine whey.
    Biotechnol Prog 2017 Jan 29;33(1):171-180. Epub 2016 Nov 29.
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Biotecnología, Junín 956 (1113), Buenos Aires, Argentina.
    Casein glycomacropeptide (CMP) is a 64- amino acid peptide found in cheese whey, which is released after κ-casein specific cleavage by chymosin. CMP lacks aromatic amino acids, a characteristic that makes it usable as a nutritional supplement for people with phenylketonuria. CMP consists of two nonglycosylated isoforms (aCMP A and aCMP B) and its different glycosylated forms (gCMP A and gCMP B). Read More

    Analysis of the functional muscle-bone unit of the forearm in patients with phenylketonuria by peripheral quantitative computed tomography.
    J Inherit Metab Dis 2017 Mar 22;40(2):219-226. Epub 2016 Nov 22.
    Department of Pediatrics I, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
    Bone disease in patients with phenylketonuria (PKU) is incompletely characterized. We therefore analyzed, in a cross-sectional study radius macroscopic bone architecture and forearm muscle size by peripheral quantitative computed tomography (pQCT) and muscle strength by hand dynamometry in a large cohort (n = 56) of adolescent and adult patients with PKU aged 26.0 ± 8. Read More

    [Phenotypic and molecular characterization of a Colombian family with phenylketonuria].
    Biomedica 2016 Sep 1;36(3):390-396. Epub 2016 Sep 1.
    Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.
    Introduction: Phenylketonuria is a metabolic disorder characterized by severe neurological involvement and behavioral disorder, whose early diagnosis enables an effective treatment to avoid disease sequelae, thus changing the prognosis. Objective: To characterize a family with phenylketonuria in Colombia at clinical, biochemical and molecular levels. Materials and methods: The population consisted of seven individuals of a consanguineous family with four children with suggestive symptoms of phenylketonuria. Read More

    Designing medical foods for inherited metabolic disorders: why intact protein is superior to amino acids.
    Curr Opin Biotechnol 2016 Nov 8;44:39-45. Epub 2016 Nov 8.
    Department of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USA.
    Phenylketonuria and tyrosinemia are inherited metabolic disorders characterized by high blood levels of phenylalanine (Phe) or tyrosine (Tyr), due to mutations in genes affecting Phe and Tyr metabolism, respectively. The primary management is a lifelong diet restricted in protein from natural foods in combination with medical foods comprised mixtures of synthetic amino acids. Compliance is often poor after childhood leading to neuropsychological sequela. Read More

    Household financial burden of phenylketonuria and its impact on treatment in China: a cross-sectional study.
    J Inherit Metab Dis 2016 Nov 10. Epub 2016 Nov 10.
    Department of Pediatrics, China-Japan Friendship Hospital, No. 2, Yinghua East Street, Chaoyang District, Beijing, 100029, China.
    Background: Phenylketonuria (PKU) is a rare inborn disease, which, untreated, leading to severe neurobehavioral dysfunction. Considering its complexity, the management of PKU may bring a formidable economic burden to parents and caregivers. It is still unknown what the out-of-pocket expenses are for a patient with PKU in China. Read More

    The first Mongolian cases of phenylketonuria in selective screening of inborn errors of metabolism.
    Mol Genet Metab Rep 2016 Dec 28;9:71-74. Epub 2016 Oct 28.
    Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan.
    Background: Inborn errors of metabolism (IEM) are rare genetic disorders in which a single gene defect causes a clinically significant block in a metabolic pathway. Clinical problems arise due to either accumulation of substrates that are toxic or interfere with normal function, or deficiency of the products that are used to synthesize essential compounds. There is no report of screening results or confirmed cases of IEM in Mongolia. Read More

    Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria.
    Dev Neuropsychol 2016 May-Jun;41(4):245-260. Epub 2016 Nov 2.
    c BioMarin Pharmaceutical Inc ., Novato , California.
    This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperactivity, depression, and anxiety. Read More

    Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.
    Am J Clin Nutr 2016 Nov 21;104(5):1292-1300. Epub 2016 Sep 21.
    University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, Netherlands;
    Background: Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established.

    Objective: In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Read More

    Screening for inherited metabolic diseases using gas chromatography-tandem mass spectrometry (GC-MS/MS) in Sichuan, China.
    Biomed Chromatogr 2017 Apr 1;31(4). Epub 2016 Nov 1.
    Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Sichuan, China.
    The aim of this study was to retrospectively diagnose and confirm inherited metabolic diseases (IMD), from a small population of IMD high-risk patients, with the aid of gas chromatography-tandem mass spectrometry (GC-MS/MS), technologies yet to be popularized in Sichuan, China. Using GC-MS/MS coupled with clinical diagnosis, we retrospectively analyzed samples of dried blood spots and urine specimen from 183 IMD high-risk infant patients, who visited the West China Second Hospital of Sichuan University between June 2013 and October 2015. Four out of 183 IMD high-risk infant patients were finally diagnosed to be IMD positive, among which two patients were identified with phenylketonuria, one with maple syrup urine disease, and 1 with methylmalonic academia. Read More

    Newborn screening: a review of history, recent advancements, and future perspectives in the era of next generation sequencing.
    Curr Opin Pediatr 2016 Dec;28(6):694-699
    Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
    Purpose Of Review: The purpose of this review is to summarize the development and recent advancements of newborn screening.

    Recent Findings: Early initiation of medical care has modified the outcome for many disorders that were previously associated with high morbidity (such as cystic fibrosis, primary immune deficiencies, and inborn errors of metabolism) or with significant neurodevelopmental disabilities (such as phenylketonuria and congenital hypothyroidism). The new era of mass spectrometry and next generation sequencing enables the expansion of the newborn screen panel, and will help to address technical issues such as turnaround time, and decreasing false-positive and false-negative rates for the testing. Read More

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