8,280 results match your criteria Phenylketonuria

Sapropterin For Phenylketonuria: A Japanese Post-Marketing Surveillance Study.

Pediatr Int 2021 Jul 31. Epub 2021 Jul 31.

Daiichi Sankyo Company Limited, 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan.

Background: To assess the long-term safety and efficacy of sapropterin in a real-world setting in Japanese patients with tetrahydrobiopterin (BH4)-responsive phenylketonuria (PKU).

Methods: This post-marketing surveillance study enrolled all patients in Japan with confirmed BH4-responsive PKU who were administrated sapropterin between July 2008 and October 2017. Patients were observed at least every 3 months during follow-up, with key data collected on treatment exposure/duration, effectiveness according to physician judgement, serum phenylalanine levels, and adverse events. Read More

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Motor control and learning in individuals with early-treated phenylketonuria.

Neuropsychology 2021 Jul 29. Epub 2021 Jul 29.

Department of Psychological Sciences.

Objective: Although past studies have documented motor control impairments in individuals with early-treated phenylketonuria (ETPKU), much less is known regarding motor learning in ETPKU. The goal of the present study was to advance our understanding on this front.

Method: We isolated and examined motor kinematics associated with the learning of a rapid aimed limb movement in a sample of 40 individuals (13-34 years of age) with ETPKU and a matched comparison group of 40 individuals without phenylketonuria (PKU). Read More

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Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study.

Nat Metab 2021 Jul 22. Epub 2021 Jul 22.

Synlogic, Inc., Cambridge, MA, USA.

Phenylketonuria (PKU) is a rare disease caused by biallelic mutations in the PAH gene that result in an inability to convert phenylalanine (Phe) to tyrosine, elevated blood Phe levels and severe neurological complications if untreated. Most patients are unable to adhere to the protein-restricted diet, and thus do not achieve target blood Phe levels. We engineered a strain of E. Read More

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Development of a mechanistic model to predict synthetic biotic activity in healthy volunteers and patients with phenylketonuria.

Commun Biol 2021 Jul 22;4(1):898. Epub 2021 Jul 22.

Synlogic, Inc., Cambridge, MA, USA.

The development of therapeutics depends on predictions of clinical activity from pre-clinical data. We have previously described SYNB1618, an engineered bacterial therapeutic (synthetic biotic) for the treatment of Phenylketonuria (PKU), a rare genetic disease that leads to accumulation of plasma phenylalanine (Phe) and severe neurological complications. SYNB1618 consumes Phe in preclinical models, healthy human volunteers, and PKU patients. Read More

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Extremely low birthweight neonates with phenylketonuria require special dietary management.

Acta Paediatr 2021 Jul 21. Epub 2021 Jul 21.

Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic.

Aim: Extremely low birthweight (ELBW) neonates require a high protein intake, but this can be challenging in the very rare cases when they also have phenylketonuria (PKU). This is due to a lack of suitable parenteral nutrition or enteral formula. Our aim was to analyse tolerance to phenylalanine in these infants. Read More

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Clinical and Paraclinical Characteristics of Non-Classic Phenylketonuria.

Iran J Child Neurol 2021 ;15(3):131-138

Pediatric Resident Endocrinology and Metabolism, Mofid Children's Hospital, Shahid Beheshti Unversity of Medical Sciences, Tehran, Iran.

Objective: Phenylketonuria (PKU) is one of the most common inherited metabolic diseases, which is classified into classic and non-classic types. It is estimated that 2% of children with PKU develop a severe and progressive neurological disease, called non-classic (malignant) PKU. This study aimed to demonstrate the clinical features, laboratory findings, and diagnostic/therapeutic characteristics of non-classic PKU patients referred to a tertiary referral center for children in Tehran, Iran. Read More

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January 2021

Core Outcome Sets for Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Phenylketonuria.

Pediatrics 2021 Jul 15. Epub 2021 Jul 15.

Department of Psychiatry, University of Toronto, Toronto, Canada.

Background: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies.

Methods: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Read More

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Selective adsorption of egg white hydrolysates onto activated carbon: Establishment of physicochemical mechanisms for removing phenylalanine.

Food Chem 2021 Jun 4;364:130285. Epub 2021 Jun 4.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu 214122, China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address:

Previously, it was shown that activated carbon can remove phenylalanine from egg white hydrolysates to produce a low phenylalanine peptide ingredient that can be used by individuals suffering from phenylketonuria. However, the factors impacting the selective adsorption of phenylalanine and peptides to activated carbon is not fully understood, which is holding back the optimization of this process. In this research, two activated carbons with different morphologies and electrical characteristics were used to adsorb egg white hydrolysates with different degrees of hydrolysis. Read More

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Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing.

Hum Mutat 2021 Jul 7. Epub 2021 Jul 7.

Gene Solutions, Ho Chi Minh City, Vietnam.

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Read More

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A Retrospective Case Series Analysis of the Relationship Between Phenylalanine: Tyrosine Ratio and Cerebral Glucose Metabolism in Classical Phenylketonuria and Hyperphenylalaninemia.

Front Neurosci 2021 17;15:664525. Epub 2021 Jun 17.

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

We retrospectively examined the relationship between blood biomarkers, in particular the historical mean phenylalanine to tyrosine (Phe:Tyr) ratio, and cerebral glucose metabolism. We hypothesized that the historical mean Phe:Tyr ratio would be more predictive of cerebral glucose metabolism than the phenylalanine (Phe) level alone. We performed a retrospective case series analysis involving 11 adult classical phenylketonuria/hyperphenylalaninemia patients under the care of an Inherited Metabolic & Neuropsychiatry Clinic who had complained of memory problems, collating casenote data from blood biochemistry, and clinical [F]fluorodeoxyglucose positron emission tomography ([F]FDG PET). Read More

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L-carnitine protects DNA oxidative damage induced by phenylalanine and its keto acid derivatives in neural cells: a possible pathomechanism and adjuvant therapy for brain injury in phenylketonuria.

Metab Brain Dis 2021 Jul 3. Epub 2021 Jul 3.

Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Although phenylalanine (Phe) is known to be neurotoxic in phenylketonuria (PKU), its exact pathogenetic mechanisms of brain damage are still poorly known. Furthermore, much less is known about the role of the Phe derivatives phenylacetic (PAA), phenyllactic (PLA) and phenylpyruvic (PPA) acids that also accumulate in this this disorder on PKU neuropathology. Previous in vitro and in vivo studies have shown that Phe elicits oxidative stress in brain of rodents and that this deleterious process also occurs in peripheral tissues of phenylketonuric patients. Read More

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Thirty-Year Lessons from the Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in Japan.

Int J Neonatal Screen 2021 Jun 29;7(3). Epub 2021 Jun 29.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.

Congenital adrenal hyperplasia (CAH) is an inherited disorder caused by the absence or severely impaired activity of steroidogenic enzymes involved in cortisol biosynthesis. More than 90% of cases result from 21-hydroxylase deficiency (21OHD). To prevent life-threatening adrenal crisis and to help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH have been introduced in numerous countries. Read More

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Unravelling the Complex Denaturant and Thermal-Induced Unfolding Equilibria of Human Phenylalanine Hydroxylase.

Int J Mol Sci 2021 Jun 18;22(12). Epub 2021 Jun 18.

Departamento de Bioquímica y Biología Molecular y Celular, Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Units: BIFI-IQFR (CSIC) and GBsC-CSIC, University of Zaragoza, 50009 Zaragoza, Spain.

Human phenylalanine hydroxylase (PAH) is a metabolic enzyme involved in the catabolism of L-Phe in liver. Loss of conformational stability and decreased enzymatic activity in PAH variants result in the autosomal recessive disorder phenylketonuria (PKU), characterized by developmental and psychological problems if not treated early. One current therapeutic approach to treat PKU is based on pharmacological chaperones (PCs), small molecules that can displace the folding equilibrium of unstable PAH variants toward the native state, thereby rescuing the physiological function of the enzyme. Read More

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The Impact of the First 2020 COVID-19 Lockdown on the Metabolic Control of Patients with Phenylketonuria.

Nutrients 2021 Jun 12;13(6). Epub 2021 Jun 12.

Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznań, Poland.

The present study assessed patients' metabolic control of phenylketonuria (PKU) during the first 2020 COVID-19 lockdown in Poland. Blood (phenylalanine) Phe results of the tests of 535 patients, performed in 2019 and in the first months of 2020, were analysed. The six-week lockdown period was compared to the preceding six-week period as well as to the two corresponding periods of 2019 (three non-lockdown periods). Read More

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A Three-Year Longitudinal Study Comparing Bone Mass, Density, and Geometry Measured by DXA, pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes.

Nutrients 2021 Jun 17;13(6). Epub 2021 Jun 17.

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

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm.

Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source.

Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11. Read More

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Aspartame-True or False? Narrative Review of Safety Analysis of General Use in Products.

Nutrients 2021 Jun 7;13(6). Epub 2021 Jun 7.

Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Read More

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The Impact of the COVID-19 Pandemic on the Perception of Health and Treatment-Related Issues among Patients with Phenylketonuria in Poland-The Results of a National Online Survey.

Int J Environ Res Public Health 2021 06 13;18(12). Epub 2021 Jun 13.

Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

There is agreement that the pandemic has affected the healthcare system and behaviour of patients. This study aims to identify problems encountered by patients with phenylketonuria (PKU) and their parents/caregivers during the six-week pandemic lockdown in Poland (15 March to 30 April 2020). To determine the factors that influenced health and treatment-related issues, as well as the respondents' perception of the impact of the pandemic, study participants were asked to complete a non-validated online questionnaire comprising 31 questions (including 27 single-choice, two multiple-choice and two open-ended ones). Read More

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Ethical implications of next-generation sequencing and the future of newborn screening.

J Am Assoc Nurse Pract 2021 Jun 30;33(7):492-495. Epub 2021 Jun 30.

Texas A&M University-Corpus Christi, Corpus Christi, Texas.

Abstract: Over the last 50 years, routine newborn blood screening for congenital disorders has been hailed as a miracle of modern science, saving countless lives by providing a means to detect and treat life-threatening disorders before symptoms present. Despite progress made with more than 5,000 babies effectively identified with rare conditions each year, congenital anomalies collectively remain at the top of the list as the cause of death for babies under 1 year of age, accounting for more than 20% of all infant mortalities. Rapid technological advances have seen the original singular newborn screen for phenylketonuria expand to a core set of 34 conditions and an additional 26 secondary conditions on the Recommended Uniform Screening Panel, with wide state-to-state variation for implementation. Read More

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Retraction notice to "Sustaining benefits of nutritional therapy in young adults with phenylketonuria - A 2 year prospective study" [Molecular Genetics and Metabolism Reports 22 (2020) 100573].

Johannes Krämer

Mol Genet Metab Rep 2021 Jun 6;27:100752. Epub 2021 Apr 6.

Division of Inborn Errors of Metabolism, Children's Hospital, University of Ulm, Ulm, Germany.

[This retracts the article DOI: 10.1016/j.ymgmr. Read More

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Retraction notice to "Case-control study about the acceptance of Pegvaliase in Phenylketonuria" Molecular Genetics and Metabolism Reports 22 (2020) 100557.

Johannes Krämer

Mol Genet Metab Rep 2021 Jun 31;27:100750. Epub 2021 Mar 31.

Division of Inborn Errors of Metabolism, Children's Hospital, University of Ulm, Ulm, Germany.

[This retracts the article DOI: 10.1016/j.ymgmr. Read More

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Milestones in treatments for inborn errors of metabolism: Reflections on Where chemistry and medicine meet.

Am J Med Genet A 2021 Jun 24. Epub 2021 Jun 24.

Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.

From Sir Archibald Garrod's initial description of the tetrad of albinism, alkaptonuria, cystinuria, and pentosuria to today, the field of medicine dedicated to inborn errors of metabolism has evolved from disease identification and mechanistic discovery to the development of therapies designed to subvert biochemical defects. In this review, we highlight major milestones in the treatment and diagnosis of inborn errors of metabolism, starting with dietary therapy for phenylketonuria in the 1950s and 1960s, and ending with current approaches in genetic manipulation. Read More

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Novel vectors and approaches for gene therapy in liver diseases.

JHEP Rep 2021 Aug 30;3(4):100300. Epub 2021 Apr 30.

Gene Therapy Area, Foundation for Applied Medical Research, University of Navarra, IdisNA, Pamplona, Spain.

Gene therapy is becoming an increasingly valuable tool to treat many genetic diseases with no or limited treatment options. This is the case for hundreds of monogenic metabolic disorders of hepatic origin, for which liver transplantation remains the only cure. Furthermore, the liver contains 10-15% of the body's total blood volume, making it ideal for use as a factory to secrete proteins into the circulation. Read More

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Monitoring Metabolites Using an NAD(P)H-sensitive Polymer Dot and a Metabolite-Specific Enzyme.

Angew Chem Int Ed Engl 2021 Jun 19. Epub 2021 Jun 19.

Department of Chemistry and Bioengineering, University of Washington, Seattle, WA, 98195, USA.

We introduce an NAD(P)H-sensitive polymer dot (Pdot) biosensor for point-of-care monitoring of metabolites. The Pdot is combined with a metabolite-specific NAD(P)H-dependent enzyme that catalyzes the oxidation of the metabolite, generating NAD(P)H. Upon UV illumination, the NAD(P)H quenches the fluorescence emission of Pdot at 627 nm via electron transfer, and also fluoresces at 458 nm, resulting in a shift from red to blue emission at higher NAD(P)H concentrations. Read More

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Long-term cognitive and psychosocial outcomes in adults with phenylketonuria.

J Inherit Metab Dis 2021 Jun 18. Epub 2021 Jun 18.

Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London.

Previous studies have suggested that cognitive and psychosocial underfunctioning in early-treated adults with PKU may be explained by suboptimal adherence to dietary treatments, however these studies often employ small samples, with different outcome measures, definitions and cut-offs. Samples have also tended to comprise participants with a limited range of blood phenylalanine concentrations, and often individuals who may not have been treated early enough to avoid neurological damage. In this study, we explore the impact of lifetime dietary control, as indicated by blood phenylalanine concentrations in childhood, adolescence and adulthood, on long-term cognitive and psychosocial outcomes in a large sample of adults with PKU who were diagnosed by neonatal screening and commenced on dietary treatment within the first month of life. Read More

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Overweight/obesity in adolescents with phenylketonuria: Protective and predisposing factors.

J Pediatr (Rio J) 2021 Jun 16. Epub 2021 Jun 16.

Universidade Federal de Minas Gerais (UFMG), Faculdade de Medicina, Departamento de Pediatria, Belo Horizonte, MG, Brazil.

Objective: To estimate the prevalence and factors associated with overweight/obesity development in adolescents with early diagnosed phenylketonuria treated exclusively by diet.

Methodology: In this cross-sectional study anthropometric measurements, serum phenylalanine levels, and 10 metabolites associated with lipid and carbohydrate metabolism were analyzed in 101 adolescents aged 10-20 years. Adolescents were categorized into overweight/obesity and eutrophic/low body mass index groups. Read More

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The History of Pediatric and Adult Hearing Screening.

Robert J Ruben

Laryngoscope 2021 Jun 18. Epub 2021 Jun 18.

Departments of Otolaryngology - Head and neck Surgery and Pediatrics, Albert Einstein College of Medicine - Montefiore Medical Center, New York, New York, U.S.A.

Objectives/hypothesis: To document the history of hearing seeing in children and adults.

Study Design: A literature search in all languages was carried out with the terms of hearing screening from the following sources: Pub Med, Science Direct, World Catalog, Index Medicus, Google scholar, Google Books, National Library of Medicine, Welcome historical library and The Library of Congress.

Methods: The primary sources consisting of books, scientific reports, public documents, governmental reports, and other written material were analyzed to document the history of hearing screening. Read More

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Serendipitous discovery of phenylketonuria in Iraq - How to identify and treat?

Mol Genet Metab Rep 2021 Jun 13;27:100737. Epub 2021 Mar 13.

3:1 Neuropsychology Consultants, PLLC, United States of America.

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Next-Generation Sequencing in Newborn Screening: A Review of Current State.

Front Genet 2021 26;12:662254. Epub 2021 May 26.

Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.

Newborn screening was first introduced at the beginning of the 1960s with the successful implementation of the first phenylketonuria screening programs. Early expansion of the included disorders was slow because each additional disorder screened required a separate test. Subsequently, the technological advancements of biochemical methodology enabled the scaling-up of newborn screening, most notably with the implementation of tandem mass spectrometry. Read More

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Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Front Neurosci 2021 28;15:673600. Epub 2021 May 28.

Department of Paediatrics, University Hospital Center Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia.

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes-MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis. Read More

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Nutrition status of adults with phenylketonuria treated with pegvaliase.

Mol Genet Metab 2021 Aug 7;133(4):345-351. Epub 2021 Jun 7.

Met Ed, Boulder, CO 80302, United States.

Background: Pegvaliase is an enzyme substitution therapy that reduces blood phenylalanine (Phe) in adults with phenylketonuria (PKU), and often allows normalization of protein intake (≥0.8 g protein/kg). Here we examine the nutrition status of adults with PKU consuming a normal protein intake without medical food after being treated with pegvaliase for ≥1 year. Read More

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