7,771 results match your criteria Phenylketonuria
Genet Med 2018 Dec 14. Epub 2018 Dec 14.
Departments of Molecular and Medical Genetics and Pediatrics, Oregon Health & Science University, Portland, OR, USA.
Purpose: Phenylketonuria (PKU) is a rare metabolic disorder that requires life-long management to reduce phenylalanine (Phe) concentrations within the recommended range. The availability of pegvaliase (PALYNZIQ™, an enzyme that can metabolize Phe) as a new therapy necessitates the provision of guidance for its use.
Methods: A Steering Committee comprising 17 health-care professionals with experience in using pegvaliase through the clinical development program drafted guidance statements during a series of face-to-face meetings. Read More
Nutrients 2018 Dec 7;10(12). Epub 2018 Dec 7.
Division Metabolic and Nutritional Medicine, LMU-Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children's Hospital, 80337 Munich, Germany.
Children with phenylketonuria (PKU) follow a protein restricted diet with negligible amounts of docosahexaenoic acid (DHA). Low DHA intakes might explain subtle neurological deficits in PKU. We studied whether a DHA supply modified plasma DHA and neurological and intellectual functioning in PKU. Read More
Nutrition 2018 Aug 20;59:180-181. Epub 2018 Aug 20.
Department of Pediatrics, Hospital Universitario Rio Hortega, Valladolid, Spain.
Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (phe) metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase that converts phe into tyrosine. If left untreated, PKU results in increased phe concentrations in the blood and in the brain, which cause severe intellectual disability, epilepsy, and behavioral problems. These disorders can be prevented if a diet low in phe is introduced. Read More
Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2018 Dec;35(6):791-795
Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450002, China.
Objective: To explore the characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province.
Methods: The 13 exons of the PAH gene were subjected to PCR amplification and direct sequencing. Large fragment deletion and duplication of the PAH gene were detected with a multiple ligation-dependent probe amplification (MLPA) assay. Read More
3 Biotech 2018 Dec 16;8(12):488. Epub 2018 Nov 16.
1Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
double mutant (C503S/C565S) phenylalanine ammonia-lyase (PAL) is an appealing enzyme in the enzyme-replacement therapy of phenylketonuria. Yet abundant production of this enzyme has been of concern for industrial production. In this study, we have characterized 1175 bacterial signal peptides (SPs) and identified the most efficient ones for the excretory production of mutant AvPAL. Read More
Sci Rep 2018 Nov 20;8(1):17137. Epub 2018 Nov 20.
Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Phenylalanine hydroxylase deficiency (PAHD), one of the genetic disorders resulting in hyperphenylalaninemia, has a complex phenotype with many variants and genotypes among different populations. Here, we describe the mutational and phenotypic spectrum of PAHD in a cohort of 420 patients from neonatal screening between 1999 and 2016. The observed phenotypes comprised 43. Read More
Nutrients 2018 Nov 18;10(11). Epub 2018 Nov 18.
Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal.
In phenylketonuria (PKU), synthetic protein derived from L-amino acids (AAs) is essential in a low-phenylalanine (Phe) diet. Glycomacropeptide (GMP), an intact protein, is very low in Phe in its native form. It has been modified and adapted for PKU to provide an alternative protein source through supplementation with rate-limiting amino acids (GMP-AAs), although it still contains residual Phe. Read More
Mol Genet Metab Rep 2018 Dec 2;17:64-68. Epub 2018 Nov 2.
Birmingham Women's & Children's NHS Trust, Birmingham, United Kingdom.
Introduction: Many women with PKU are well-informed about the risks of maternal PKU but there are several barriers to achieving satisfactory metabolic control before and during pregnancy. Many studies have documented the outcome of maternal PKU infants, but very little has been reported about the experiences of women of reproductive age with PKU, particularly about their psychosexual development, pre-conception, pregnancy and postnatal experience.
Methods: In the UK, in a subsection of an online questionnaire conducted by the National Society for PKU (NSPKU) about living with PKU, women aged 18 years and over completed 9 closed questions about their pre-conception, pregnancy and post-natal experiences and an open-ended question on their reproductive health. Read More
Eur J Med Genet 2018 Oct 30. Epub 2018 Oct 30.
Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, IR, Iran. Electronic address:
Phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene. After thalassemia, PKU is considered as the most common autosomal recessive diseases in the Iranian population. Therefore, an efficient diagnostic strategy is required to identify disease-causing mutations in this population. Read More
Med Sci Monit 2018 Oct 30;24:7759-7769. Epub 2018 Oct 30.
Institute of Childcare and Pediatrics "Martagão Gesteira", Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
BACKGROUND Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene. When untreated, PKU leads to a significant intellectual deficiency. Although early initiation of dietary therapy allows normal cognitive development, low adherence to treatment may result in neuropsychological deficits, including attention problems. Read More
Orphanet J Rare Dis 2018 Oct 30;13(1):192. Epub 2018 Oct 30.
Department of Human Genetics, Metabolic Nutrition Program, Emory University School of Medicine, Atlanta, GA, USA.
Background: People with Phenylketonuria (PKU) who respond to tetrahydrobiopterin (BH4) often decrease dependence on medical food (MF) following increased phenylalanine (phe) tolerance. Responders to BH4 may experience a reduction in certain nutrients if not compensated through intact foods or supplements. This study investigated B6, B12, folate, and iron status based on blood levels and dietary intake in patients with PKU responsive to BH4 over 1 year. Read More
Orphanet J Rare Dis 2018 Oct 26;13(1):188. Epub 2018 Oct 26.
Neuropediatric Department, PKU Follow Up Unit, Hospital Sant Joan de Déu (HSJD), Institut de Recerca Sant Joan de Deu (IRSJD), Passeig Sant Joan de Deu 2, Postal code, 08950, Barcelona, Spain.
Background: Despite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)).
Methods: DTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Read More
EBioMedicine 2018 Nov 23;37:366-373. Epub 2018 Oct 23.
BioMarin Pharmaceutical Inc., 105 Digital Dr, Novato, CA 94949, United States.
Background: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy.
Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Read More
Mol Genet Metab Rep 2018 Dec 18;17:57-63. Epub 2018 Oct 18.
Birmingham Women's & Children's NHS Trust, Birmingham, United Kingdom.
Introduction: We report the practical, social and psychological issues of living with phenylketonuria (PKU) from one of the largest surveys that has been completed by both adults with PKU and parents/caregivers of children.
Methods: In the UK, parents/caregivers of children and adults with PKU were invited to complete an online survey between November 2017 to January 2018 by the NSPKU (National Society for Phenylketonuria).
Results: 631 participants (adults, = 338; parents/caregivers of children, = 293) with PKU completed the questionnaire. Read More
Nutr Neurosci 2018 Oct 25:1-12. Epub 2018 Oct 25.
c Institute of Child Health Agia Sofia Children's Hospital , Athens , Greece.
Phenylalanine hydroxylase (PAH) deficiency, commonly named phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism inherited with an autosomal recessive trait. It is characterized by high blood and cerebral Phe levels, resulting in intellectual disabilities, seizures, etc. Early diagnosis and treatment of the patients prevent major neuro-cognitive deficits. Read More
JPEN J Parenter Enteral Nutr 2018 Oct 24. Epub 2018 Oct 24.
Social and Behavioral Research Branch, Social Network Methods Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Background: Propionic acidemia (PA), an autosomal recessive metabolic disorder, has an estimated incidence of 1:105,000-130,000 in the United States. Nutrition management is a main intervention for PA. Research in inborn errors of metabolism such as phenylketonuria has identified association of parental perceptions and practices with dietary outcomes. Read More
Pediatr Int 2018 Oct;60(10):985-986
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Br J Pharmacol 2018 Oct 19. Epub 2018 Oct 19.
Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary.
Background And Purpose: Homocystinurias are rare genetic defects characterized by altered fluxes of sulfur compounds including homocysteine and cysteine. We explored whether the severely perturbed sulfur amino acid metabolism in patients with homocystinurias affects the metabolism of hydrogen sulfide.
Experimental Approach: We studied 10 treated patients with a block in the conversion of homocysteine to cysteine due to cystathionine β-synthase deficiency (CBSD) and six treated patients with remethylation defects (RMD) and an enhanced flux of sulfur metabolites via transsulfuration. Read More
Methods Mol Biol 2019 ;1873:279-292
Department of Biomedicine, University of Bergen, Bergen, Norway.
Pharmacological chaperones are small molecular weight molecules that bind specifically to protein targets and stabilize unstable and misfolded conformations. In particular, there is an increasing interest in the application of this type of compounds for the correction of genetic conformational disorders, which are caused by mutations leading to protein instability. The discovery of compounds with pharmacological chaperone ability is customarily initiated by a high-throughput screening of chemical libraries searching for stabilizing binders. Read More
Anal Chim Acta 2018 Dec 29;1041:108-113. Epub 2018 Aug 29.
Department of Chemistry, National Taiwan Normal University, Taiwan. Electronic address:
Clinicians require a simple quantitative method for the detection of both phenylalanine and tyrosine to facilitate the diagnosis of phenylketonuria, a common inherited disorder of amino acid metabolism. In this study, we developed a novel whole-cell biosensor for the quantification of phenylalanine and tyrosine through the expression of red and green fluorescent proteins. The proposed system responds specifically and sensitively to phenylalanine/tyrosine without interferences from other amino acids. Read More
Pediatr Res 2018 Oct 17. Epub 2018 Oct 17.
Neonatal Research Group, Health Research Institute La Fe, Valencia, Spain.
Despite a strict dietary control, patient with hyperphenylalaninemia or phenylketonuria may show cognitive and/or behavioral disorders. These comorbid deficits are of great concern to patients, families, and health organizations. However, biomarkers capable of detecting initial stages of neurological damage are not commonly employed. Read More
Neuropsychiatr Dis Treat 2018 5;14:2551-2561. Epub 2018 Oct 5.
Public Health and Community Medicine Department, Faculty of Medicine, Sohag University, Sohag, Egypt.
Background: Phenylketonuria (PKU) is considered to be a rare inborn error of metabolism but one of the commonest causes of mental retardation if untreated.
Objectives: The present study was done to characterize the clinical patterns of PKU and analyze various neuropsychiatric outcomes in PKU children in Sohag Province, Egypt.
Patients And Methods: A prospective cohort study was conducted on 113 PKU patients, diagnosed during the period from 2012 to 2017, at the Pediatric Neurology Clinic of Sohag University Hospital, Upper Egypt. Read More
Foods 2018 Oct 9;7(10). Epub 2018 Oct 9.
Department of Chemical and Biological Engineering, University of Wisconsin, 1605 Linden Dr., Madison, WI 53706, USA.
Fractionation of the bovine glycomacropeptide (GMP) from the other proteins in cheese whey was examined using ultrafiltration membranes surface modified to contain positively charged polymer brushes made of polyhexamethylene biguanide. By placing a strong positive charge on a 1000 kDa ultrafiltration membrane and adjusting the pH of whey close to the isoelectric point of GMP, a 14-fold increase in selectivity was observed compared to unmodified membranes. A one stage membrane system gave 90% pure GMP and a three-stage rectification system gave 97% pure GMP. Read More
J Child Adolesc Psychiatr Nurs 2018 Oct 8;31(2-3):48-52. Epub 2018 Oct 8.
Nursing Research Center, Kerman University of Medical Science, Kerman, Iran.
Background: Phenylketonuria is a hereditary disease caused by the lack or deficiency of phenylalanine hydroxylase enzyme activity. Parents of children with phenylketonuria undergo significant stress during their childcare years. They are also responsible for controlling their children's dietary treatment and this may affect their quality of life. Read More
Nat Med 2018 Oct 8;24(10):1519-1525. Epub 2018 Oct 8.
Department Biology, Institute for Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
CRISPR-Cas-based genome editing holds great promise for targeting genetic disorders, including inborn errors of hepatocyte metabolism. Precise correction of disease-causing mutations in adult tissues in vivo, however, is challenging. It requires repair of Cas9-induced double-stranded DNA (dsDNA) breaks by homology-directed mechanisms, which are highly inefficient in nondividing cells. Read More
J Biol Chem 2018 Oct 4. Epub 2018 Oct 4.
Department of Chemistry, Temple University, United States.
Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed in genetic disorders leading to hyperphenylalaninemia and phenylketonuria. PAH senses elevated Phe concentrations by transient allosteric Phe binding to a protein-protein interface between ACT domains of different subunits in a PAH tetramer. This interface is present in an activated PAH tetramer (A-PAH) and absent in a resting-state PAH tetramer (RS-PAH). Read More
Nutr Res Rev 2018 Oct 4:1-9. Epub 2018 Oct 4.
7Division of Metabolic Diseases,Beatrix Children's Hospital,University Medical Center Groningen,University of Groningen,Groningen,the Netherlands.
It has been nearly 70 years since the discovery that strict adherence to a diet low in phenylalanine prevents severe neurological sequelae in patients with phenylalanine hydroxylase deficiency (phenylketonuria; PKU). Today, dietary treatment with restricted phenylalanine intake supplemented with non-phenylalanine amino acids to support growth and maintain a healthy body composition remains the mainstay of therapy. However, a better understanding is needed of the factors that influence N balance in the context of amino acid supplementation. Read More
Orphanet J Rare Dis 2018 Sep 29;13(1):173. Epub 2018 Sep 29.
Department of Pediatrics, Hôpital d'Enfants Brabois, CHU Nancy, Vandoeuvre les Nancy, France.
Background: Treatment of phenylketonuria (PKU) with sapropterin dihydrochloride in responsive patients from an early age can have many advantages for the patient over dietary restriction alone. Accordingly, approval of sapropterin in the European Union was extended in 2015 to include patients aged 0-4 years, bringing the treatment age range in line with that in the USA and providing an additional treatment option for those patients with PKU who are responsive or partially responsive to treatment with sapropterin. Subsequently, European guidelines have been published on the diagnosis and management of patients with PKU. Read More
Mol Genet Metab 2018 Nov 12;125(3):228-234. Epub 2018 Sep 12.
Boston Children's Hospital and Harvard Medical School, 1 Autumn St., Rm #526, Boston, MA 02115, United States.
Background: Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU exerts a significant burden of disease. Retrospective studies using large databases allow for unique perspectives on comorbidities associated with rare diseases. Read More
Pediatr Res 2018 Sep 13. Epub 2018 Sep 13.
National PKU Alliance, Inc., Eau Claire, USA.
Curr Med Res Opin 2018 Oct 25:1-5. Epub 2018 Oct 25.
a St. John Fisher College Wegmans School of Pharmacy , Rochester , NY , USA.
Objective: In May 2018, the US Food and Drug Administration approved pegvaliase-pqpz (Palynziq*), the first enzyme substitution therapy for the treatment of phenylketonuria (PKU). This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, and the safety and tolerability profile of pegvaliase.
Methods: Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria. Read More
J Pediatr 2018 Oct;201:244
Pediatric Rheumatology Unit Shaare Zedek Medical Center Jerusalem, Israel.
J Pediatr 2018 Oct;201:121
University of Massachusetts Boston Boston, Massachusetts.
Science 2018 09;361(6407):1122-1126
Department of Chemical Biology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
Monitoring metabolites at the point of care could improve the diagnosis and management of numerous diseases. Yet for most metabolites, such assays are not available. We introduce semisynthetic, light-emitting sensor proteins for use in paper-based metabolic assays. Read More
Mol Genet Metab 2018 Nov 27;125(3):193-199. Epub 2018 Aug 27.
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Veteran's Affairs Medical Center, Pittsburgh, PA, United States.
Osteopenia is observed in some patients affected by phenylalanine hydroxylase (PAH) deficient phenylketonuria (PKU). Bone density studies, in diverse PKU patient cohorts, have demonstrated bone disease is neither fully penetrant nor uniform in bone density loss. Biochemical assessment has generated a muddled perspective regarding mechanisms of the PKU bone phenotype where the participation of hyperphenylalaninemia remains unresolved. Read More
An Pediatr (Barc) 2018 Aug 31. Epub 2018 Aug 31.
Servicio de Pediatría, Hospital de Mérida, Mérida, Badajoz, España. Electronic address:
Orphanet J Rare Dis 2018 Aug 30;13(1):150. Epub 2018 Aug 30.
School of Psychology, University of Leeds, Leeds, LS2 9JT, UK.
Background: Even though early dietary management of phenylketonuria (PKU) successfully prevents severe neurological impairments, deficits in cognitive functioning are still observed. These deficits are believed to be the result of elevated levels of phenylalanine throughout life. Research on cognitive functioning in adults with PKU (AwPKU) often focuses on domains shown to be compromised in children with PKU, such as attention and executive functions, whereas other cognitive domains have received less attention. Read More
J Inherit Metab Dis 2018 Aug 29. Epub 2018 Aug 29.
Kawsar Human Genetics Research Center, 41 Majlesi St., Vali Asr St., Tehran, 1595645513, Iran.
Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, characterized by intellectual deficit and neuropsychiatric complications in untreated patients with estimated frequency of about one in 10,000 to 15,000 live births. PAH deficiency can be detected by neonatal screening in nearly all cases with hyperphenylalaninemia on a heel prick blood spot. Molecular testing of the PAH gene can then be performed in affected family members. Read More
Med J Islam Repub Iran 2018 11;32:21. Epub 2018 Mar 11.
Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Phenylketonuria as the most common genetic metabolic disorder is the result of disruption of the phenylalanine hydroxylase gene. This study was carried out to explore the phenylalanine hydroxylase gene mutation status of Iranian phenylketonuria patients. Blood samples were collected from 30 patients, and hot spot areas of the phenylalanine hydroxylase gene, including exons 6, 7, 8, 11, and 12 were studied through polymerase chain reaction and sequencing techniques. Read More
Orphanet J Rare Dis 2018 Aug 29;13(1):149. Epub 2018 Aug 29.
University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, 9700, RB, Groningen, The Netherlands.
Background: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. Read More
Nutrients 2018 Aug 28;10(9). Epub 2018 Aug 28.
Department of Paediatrics, San Paolo Hospital, Department of Health Sciences, University of Milan, 20142 Milan, Italy.
The aim of the present study was to apply the Check-all-that-apply (CATA) method in an ambulatory context involving subjects with phenylketonuria (PKU) to obtain a sensory description and to find the drivers of liking of low-phenylalanine products (Glycomacropeptide vs. L-amino acids formulas). 86 subjects with PKU (age range: 8⁻55 years) evaluated 8 samples: 4 L-amino acid formulas and 4 Glycomacropeptide (GMP) formulas, flavored with neutral, chocolate, strawberry and tomato aromas. Read More
Mol Genet Metab 2018 Nov 23;125(3):217-227. Epub 2018 Aug 23.
Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA.
Background: Phenylketonuria (PKU) is caused by a deficiency in phenylalanine hydroxylase enzyme activity that leads to phenylalanine (Phe) accumulation in the blood and brain. Elevated blood Phe levels are associated with complications in adults, including neurological, psychiatric, and cognitive issues. Even with nutrition and pharmacological management, the majority of adults with PKU do not maintain blood Phe levels at or below guideline recommended levels. Read More
Clin Nutr ESPEN 2018 Oct 29;27:79-85. Epub 2018 Jun 29.
Ankara University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Turkey.
Background & Aims: Phenylketonuria (PKU) has a very high prevalence throughout the world. Nowadays, number of studies about impact of this metabolic disease on patients increasing. The aim of our study is to examine PKU patients' quality of life according to PKU-QOL questionnaires. Read More
Pediatr Res 2018 Aug 15. Epub 2018 Aug 15.
Faculty of Science, Division of Biochemistry, Department of Chemistry, Yuzuncu Yil University, Van, Turkey.
Background: In this study, children with phenylketonuria and healthy control subjects were assessed for glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) activity, malondialdehyde (MDA), glutathione (GSH), retinol, cholecalciferol, α-tocopherol, phylloquinone, total sialic acid (TSA), lipid bound sialic acid (LSA), total antioxidant (TAS), total oxidation (TOS), and amino acid levels, and the relationships of these variables with phenylketonuria were evaluated.
Methods: The study included 60 children with phenylketonuria and 30 control subjects. Children with phenylketonuria were divided into hyperphenylalaninemia (HPA) and amino acid mixture (AAM) groups. Read More
Can J Neurol Sci 2018 Sep 15;45(5):571-576. Epub 2018 Aug 15.
1Department of Pediatrics,Division of Clinical and Metabolic Genetics,University of Toronto,Toronto,Ontario,Canada.
We report the outcome of 12 patients with inherited neurotransmitter disorders of monoamine, tetrahydrobiopterin and γ amino butyric acid metabolisms from a single Inherited Neurotransmitter Disorder Clinic including tyrosine hydroxylase (n=2), aromatic l-amino acid decarboxylase (n=1), 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and succinic semialdehyde dehydrogenase deficiencies. Six patients (with 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and tyrosine hydroxylase deficiencies) had normal neurodevelopmental outcome on treatment. Tetrahydrobiopterin loading test in newborns with positive newborn screening for phenylketonuria will identify patients with 6-pyruvoyltetrahydropterin synthase and dihydropteridine reductase deficiencies resulting in abnormal neurotransmitter synthesis in the central nervous system in the neonatal period to initiate disease-specific treatment to improve neurodevelopmental outcome. Read More
Nat Biotechnol 2018 Oct 13;36(9):857-864. Epub 2018 Aug 13.
Synlogic Inc., Cambridge, Massachusetts, USA.
Phenylketonuria (PKU) is a genetic disease that is characterized by an inability to metabolize phenylalanine (Phe), which can result in neurotoxicity. To provide a potential alternative to a protein-restricted diet, we engineered Escherichia coli Nissle to express genes encoding Phe-metabolizing enzymes in response to anoxic conditions in the mammalian gut. Administration of our synthetic strain, SYNB1618, to the Pah PKU mouse model reduced blood Phe concentration by 38% compared with the control, independent of dietary protein intake. Read More