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1. A phase 1/2 study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B

Author

Muschol, Nicole, Koehn, Anja, von Cossel, Katharina, Okur, Ilyas, Ezgu, Fatih, Harmatz, Paul, de Castro Lopez, Maria Jose, Couce, Maria Luz, Lin, Shuan-Pei, Batzios, Spyros, Cleary, Maureen, Solano, Martha, Nestrasil, Igor, Kaufman, Brian D, Shaywitz, Adam J, Maricich, Stephen M, Kuca, Bernice, Kovalchin, Joseph, and Zanelli, Eric H

Subjects
Rare Diseases, Brain Disorders, Orphan Drug, Mucopolysaccharidoses (MPS), Neurosciences, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Humans, Mucopolysaccharidosis III, Heparitin Sulfate, Brain, Liver, Spleen, Neurological disorders, Neuroscience, Medical and Health Sciences, Immunology
Abstract

BackgroundSanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline.MethodsIn this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores.ResultsIn the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV.ConclusionAdministration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy.Trial registrationClinicaltrials.gov NCT02754076.FUNDINGBioMarin Pharmaceutical Inc. and Allievex Corporation.

Published
2023

2. A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type

Author

Muschol, Nicole, Koehn, Anja, von Cossel, Katharina, Okur, Ilyas, Ezgu, Fatih, Harmatz, Paul, Lopez, Maria J. de Castro, Couce, Maria Luz, Lin, Shuan-Pei, Batzios, Spyros, Cleary, Maureen, Solano, Martha, Nestrasil, Igor, Kaufman, Brian, Shaywitz, Adam J., Maricich, Stephen M., Kuca, Bernice, Kovalchin, Joseph, and Zanelli, Eric

Subjects
Protein therapy -- Testing, Drug delivery devices -- Testing, Mucopolysaccharidosis -- Drug therapy, Health care industry
Abstract

BACKGROUND. Sanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline. METHODS. In this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores. RESULTS. In the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV. CONCLUSION. Administration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy. TRIAL REGISTRATION. Clinicaltrials.gov NCT02754076. FUNDING. BioMarin Pharmaceutical Inc. and Allievex Corporation., Introduction Lysosomal storage diseases (LSDs) are a family of genetic disorders affecting the breakdown and recycling of complex molecules within the lysosomes (1). The lysosomal compartment contains more than 60 [...]

Published
2023
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3. Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at < 4 years of age with phenylketonuria: results of the 3-year extension of the SPARK open-label, multicentre, randomised phase IIIb trial

Author

Muntau, Ania C., Burlina, Alberto, Eyskens, François, Freisinger, Peter, Leuzzi, Vincenzo, Sivri, Hatice Serap, Gramer, Gwendolyn, Pazdírková, Renata, Cleary, Maureen, Lotz-Havla, Amelia S., Lane, Paul, Alvarez, Ignacio, and Rutsch, Frank

Published
2021
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5. The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency

Author

Keshavan, Nandaki, Abdenur, Jose, Anderson, Glenn, Assouline, Zahra, Barcia, Giulia, Bouhikbar, Lamia, Chakrapani, Anupam, Cleary, Maureen, Cohen, Marta C., Feillet, François, Fratter, Carl, Hauser, Natalie, Jacques, Tom, Lam, Amanda, McCullagh, Helen, Phadke, Rahul, Rötig, Agnès, Sharrard, Mark, Simon, Mariella, Smith, Conrad, Sommerville, Ewen W., Taylor, Robert W., Yue, Wyatt W., and Rahman, Shamima

Published
2020
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6. Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study

Author

Elkhateeb, Nour, primary, Olivieri, Giorgia, additional, Siri, Barbara, additional, Boyd, Stewart, additional, Stepien, Karolina M., additional, Sharma, Reena, additional, Morris, Andrew A. M., additional, Hartley, Thomas, additional, Crowther, Laura, additional, Grunewald, Stephanie, additional, Cleary, Maureen, additional, Mundy, Helen, additional, Chakrapani, Anupam, additional, Lachmann, Robin, additional, Murphy, Elaine, additional, Santra, Saikat, additional, Uudelepp, Mari‐Liis, additional, Yeo, Mildrid, additional, Bernhardt, Isaac, additional, Sudakhar, Sniya, additional, Chan, Alicia, additional, Mills, Philippa, additional, Ridout, Debora, additional, Gissen, Paul, additional, Dionisi‐Vici, Carlo, additional, and Baruteau, Julien, additional

Published
2023
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7. A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B.

Author

Muschol, Nicole, Muschol, Nicole, Koehn, Anja, von Cossel, Katharina, Okur, Ilyas, Ezgu, Fatih, Harmatz, Paul, de Castro Lopez, Maria J, Couce, Maria Luz, Lin, Shuan-Pei, Batzios, Spyros, Cleary, Maureen, Solano, Martha, Nestrasil, Igor, Kaufman, Brian, Shaywitz, Adam J, Maricich, Stephen M, Kuca, Bernice, Kovalchin, Joseph, Zanelli, Eric, Muschol, Nicole, Muschol, Nicole, Koehn, Anja, von Cossel, Katharina, Okur, Ilyas, Ezgu, Fatih, Harmatz, Paul, de Castro Lopez, Maria J, Couce, Maria Luz, Lin, Shuan-Pei, Batzios, Spyros, Cleary, Maureen, Solano, Martha, Nestrasil, Igor, Kaufman, Brian, Shaywitz, Adam J, Maricich, Stephen M, Kuca, Bernice, Kovalchin, Joseph, and Zanelli, Eric

Abstract

BackgroundSanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline.MethodsIn this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores.ResultsIn the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV.ConclusionAdministration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy.Trial registrationClinicaltrials.gov NCT02754076.FUNDINGBioMarin Pharmaceutical Inc. and Allievex Corporation.

Published
2023

8. Detection of neurological abnormalities in adolescents and adults with phenylketonuria

Author

Cleary, Maureen Anne

Subjects
616.3
Abstract

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt to ascertain whether the MRI abnormalities described in several adults had any clinical significance.

Published
1997
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11. Whole-genome sequencing of patients with rare diseases in a national health system

Author

Turro, Ernest, Astle, William J., Megy, Karyn, Gräf, Stefan, Greene, Daniel, Shamardina, Olga, Allen, Hana Lango, Sanchis-Juan, Alba, Frontini, Mattia, Thys, Chantal, Stephens, Jonathan, Mapeta, Rutendo, Burren, Oliver S., Downes, Kate, Haimel, Matthias, Tuna, Salih, Deevi, Sri V.V., Aitman, Timothy J., Bennett, David L., Calleja, Paul, Carss, Keren, Caulfield, Mark J., Chinnery, Patrick F., Dixon, Peter H., Gale, Daniel P., James, Roger, Koziell, Ania, Laffan, Michael A., Levine, Adam P., Maher, Eamonn R., Markus, Hugh S., Morales, Joannella, Morrell, Nicholas W., Mumford, Andrew D., Ormondroyd, Elizabeth, Rankin, Stuart, Rendon, Augusto, Richardson, Sylvia, Roberts, Irene, Roy, Noemi B.A., Saleem, Moin A., Smith, Kenneth G.C., Stark, Hannah, Tan, Rhea Y.Y., Themistocleous, Andreas C., Thrasher, Adrian J., Watkins, Hugh, Webster, Andrew R., Wilkins, Martin R., Williamson, Catherine, Whitworth, James, Humphray, Sean, Bentley, David R., Abbs, Stephen, Abulhoul, Lara, Adlard, Julian, Ahmed, Munaza, Alachkar, Hana, Allsup, David J., Almeida-King, Jeff, Ancliff, Philip, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Ashford, Sofie, Attwood, Anthony, Aurora, Paul, Babbs, Christian, Bacchelli, Chiara, Bakchoul, Tamam, Banka, Siddharth, Bariana, Tadbir, Barwell, Julian, Batista, Joana, Baxendale, Helen E., Beales, Phil L., Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Black, Graeme C., Bleda, Marta, Blesneac, Iulia, Bockenhauer, Detlef, Bogaard, Harm, Bourne, Christian J., Boyce, Sara, Bradley, John R., Bragin, Eugene, Breen, Gerome, Brennan, Paul, Brewer, Carole, Brown, Matthew, Browning, Andrew C., Browning, Michael J., Buchan, Rachel J., Buckland, Matthew S., Bueser, Teofila, Diz, Carmen Bugarin, Burn, John, Burns, Siobhan O., Burrows, Nigel, Campbell, Carolyn, Carr-White, Gerald, Casey, Ruth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Cheah, Calvin, Cheng, Floria, Chitre, Manali, Christian, Martin T., Church, Colin, Clayton-Smith, Jill, Cleary, Maureen, Brod, Naomi Clements, Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine, Collins, Peter W., Colombo, Camilla, Compton, Cecilia J., Condliffe, Robin, Cook, Stuart, Cook, H. Terence, Cooper, Nichola, Corris, Paul A A., Furnell, Abigail, Cunningham, Fiona, Curry, Nicola S., Cutler, Antony J., Daniels, Matthew J., Dattani, Mehul, Daugherty, Louise C., Davis, John, De Soyza, Anthony, Dent, Timothy, Deshpande, Charu, Dewhurst, Eleanor F., Douzgou, Sofia, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edgar, J. David M., Edwards, Karen, Egner, William, Ekani, Melanie N., Elliott, Perry, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Fassihi, Hiva, Favier, Remi, Findhammer, Jack, Fletcher, Debra, Flinter, Frances A., Floto, R. Andres, Fowler, Tom, Fox, James, Frary, Amy J., French, Courtney E., Freson, Kathleen, Gall, Henning, Ganesan, Vijeya, Gattens, Michael, Geoghegan, Claire, Gerighty, Terence S.A., Gharavi, Ali G., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Gibbs, J. Simon R., Gibson, Kate, Gilmour, Kimberly C., Girerd, Barbara, Gleadall, Nicholas S., Goddard, Sarah, Goldstein, David B., Gomez, Keith, Gordins, Pavels, Gosal, David, Graham, Jodie, Grassi, Luigi, Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip, Grigoriadou, Sofia, Grocock, Russell J., Grozeva, Detelina, Gurnell, Mark, Hackett, Scott, Hadinnapola, Charaka, Hague, William M., Hague, Rosie, Hall, Matthew, Hanson, Helen L., Haque, Eshika, Harkness, Kirsty, Harper, Andrew R., Harris, Claire L L., Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Henderson, Alex, Herwadkar, Archana, Hoffman, Jonathan, Holden, Simon, Horvath, Rita, Houlden, Henry, Houweling, Arjan C C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Joseph, Huissoon, Aarnoud P., Humbert, Marc, Hunter, Sarah, Hurles, Matthew, Irving, Melita, Izatt, Louise, Johnson, Sally A., Jolles, Stephen, Jolley, Jennifer, Josifova, Dragana, Jurkute, Neringa, Karten, Tim, Karten, Johannes, Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Kelleher, Peter, Kelly, Anne M., Kelsall, Wilf, Kempster, Carly, Kiely, David G., Kingston, Nathalie, Klima, Robert, Koelling, Nils, Kostadima, Myrto, Kovacs, Gabor, Kreuzhuber, Roman, Kuijpers, Taco W., Kumar, Ajith, Kumararatne, Dinakantha, Kurian, Manju A., Lalloo, Fiona, Lambert, Michele, Lawrie, Allan, Layton, D. Mark, Lench, Nick, Lentaigne, Claire, Lester, Tracy, Linger, Rachel, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Lyons, Paul A., Machado, Rajiv D., MacKenzie Ross, Robert V., Madan, Bella, Maimaris, Jesmeen, Malka, Samantha, Mangles, Sarah, Marchbank, Kevin J., Marks, Stephen, Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer, Mathias, Mary, Matthews, Emma, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McKinney, Harriet, McMahon, Aoife, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Mehta, Sarju G G., Michaelides, Michel, Millar, Carolyn, Mohammed, Shehla N., Moledina, Shahin, Montani, David, Moore, Anthony T., Mozere, Monika, Muir, Keith W., Nemeth, Andrea H., Newman, William G., Newnham, Michael, Noorani, Sadia, Nurden, Paquita, O’Sullivan, Jennifer, Obaji, Samya, Odhams, Chris, Okoli, Steven, Olschewski, Andrea, Olschewski, Horst, Ong, Kai Ren, Oram, S. Helen, Ouwehand, Willem H., Palles, Claire, Papadia, Sofia, Park, Soo Mi, Parry, David, Patel, Smita, Paterson, Joan, Peacock, Andrew, Pearce, Simon H H., Peden, John, Peerlinck, Kathelijne, Penkett, Christopher J., Pepke-Zaba, Joanna, Petersen, Romina, Pilkington, Clarissa, Poole, Kenneth E.S., Prathalingam, Radhika, Psaila, Bethan, Pyle, Angela, Quinton, Richard, Rahman, Shamima, Rao, Anupama, Raymond, F. Lucy, Rayner-Matthews, Paula J., Rees, Christine, Renton, Tara, Rhodes, Christopher J., Rice, Andrew S.C., Richter, Alex, Robert, Leema, Rogers, Anthony, Rose, Sarah J., Ross-Russell, Robert, Roughley, Catherine, Roy, Noemi B. A, Ruddy, Deborah M., Sadeghi-Alavijeh, Omid, Samani, Nilesh, Samarghitean, Crina, Sargur, Ravishankar B., Sarkany, Robert N., Satchell, Simon, Savic, Sinisa, Sayer, John A., Sayer, Genevieve, Scelsi, Laura, Schaefer, Andrew M., Schulman, Sol, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sen, Arjune, Sewell, W. A.Carrock, Seyres, Denis, Shah, Neil, Shapiro, Susan E., Shaw, Adam C., Short, Patrick J., Sibson, Keith, Side, Lucy, Simeoni, Ilenia, Simpson, Michael A A., Sims, Matthew C., Sivapalaratnam, Suthesh, Smedley, Damian, Smith, Katherine R., Snape, Katie, Soranzo, Nicole, Soubrier, Florent, Southgate, Laura, Spasic-Boskovic, Olivera, Staines, Simon, Staples, Emily, Steward, Charles, Stirrups, Kathleen E., Stuckey, Alex, Suntharalingam, Jay, Swietlik, Emilia M., Syrris, Petros, Tait, R. Campbell, Talks, Kate, Tate, Katie, Taylor, John M., Taylor, Jenny C., Thaventhiran, James E., Thomas, Ellen, Thomas, David, Thomas, Moira J., Thomas, Patrick, Thomson, Kate, Threadgold, Glen, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tolhuis, Bas, Tomlinson, Ian P., Toshner, Mark, Traylor, Matthew, Treacy, Carmen, Treadaway, Paul, Trembath, Richard, Turek, Wojciech, Twiss, Philip, Vale, Tom, Geet, Chris Van, Zuydam, Natalie van, Vandekuilen, Maarten, Vandersteen, Anthony M., Vazquez-Lopez, Marta, von Ziegenweidt, Julie, Vonk Noordegraaf, Anton, Wagner, Annette, Waisfisz, Quinten, Walker, Suellen M., Walker, Neil, Walter, Klaudia, Ware, James S., Watt, Christopher, Wedderburn, Lucy, Wei, Wei, Welch, Steven B., Wessels, Julie, Westbury, Sarah K., Westwood, John Paul, Wharton, John, Whitehorn, Deborah, Wilkie, Andrew O. M, Wilson, Brian T., Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R R., Wort, Stephen J., Worth, Austen, Wright, Michael, Yates, Katherine, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska, University of Cambridge [UK] (CAM), John Wyeth & Brother Limited, Medical Research Council (MRC), Wellcome Trust, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, ACS - Atherosclerosis & ischemic syndromes, Landsteiner Laboratory, Paediatric Infectious Diseases / Rheumatology / Immunology, ARD - Amsterdam Reproduction and Development, and Project, NIHR BioResource for the 100,000 Genomes

Subjects
0301 basic medicine, Erythrocytes, Internationality, Databases, Factual, National Health Programs, [SDV]Life Sciences [q-bio], Disease, VARIANTS, Genome, State Medicine, NIHR BioResource for the 100,000 Genomes Project, 0302 clinical medicine, Medicine, GATA1 Transcription Factor, Genetics, Multidisciplinary, Translational bioinformatics, ASSOCIATION, 3. Good health, Multidisciplinary Sciences, Phenotype, 030220 oncology & carcinogenesis, disease genetics, Medical genetics, Science & Technology - Other Topics, Receptors, Thrombopoietin, medicine.medical_specialty, General Science & Technology, Quantitative Trait Loci, Genomics, Computational biology, Biology, DIAGNOSIS, computational biology and bioinformatics, Actin-Related Protein 2-3 Complex, Article, LRBA, LINKS, 03 medical and health sciences, Rare Diseases, Humans, Alleles, Adaptor Proteins, Signal Transducing, Whole genome sequencing, National health, Science & Technology, Whole Genome Sequencing, MUTATIONS, business.industry, THROMBOCYTOPENIA, United Kingdom, MACROTHROMBOCYTOPENIA, genetics research, 030104 developmental biology, business, Rare disease
Abstract

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

Published
2021

12. Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

Author

Reid, Emma S., primary, Williams, Hywel, additional, Stabej, Polona Le Quesne, additional, James, Chela, additional, Ocaka, Louise, additional, Bacchelli, Chiara, additional, Footitt, Emma J., additional, Boyd, Stewart, additional, Cleary, Maureen A., additional, Mills, Philippa B., additional, and Clayton, Peter T., additional

Published
2015
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13. Coenzyme Q10 and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III

Author

Yubero, Dèlia, primary, Montero, Raquel, additional, O’Callaghan, Mar, additional, Pineda, Mercè, additional, Meavilla, Silvia, additional, Delgadillo, Veronica, additional, Sierra, Cristina, additional, Altimira, Laura, additional, Navas, Plácido, additional, Pope, Simon, additional, Oppenheim, Marcus, additional, Neergheen, Viruna, additional, Ghosh, Arunabha, additional, Mills, Phillipa, additional, Clayton, Peter, additional, Footitt, Emma, additional, Cleary, Maureen, additional, Hargreaves, Iain, additional, Jones, Simon A., additional, Heales, Simon, additional, and Artuch, Rafael, additional

Published
2015
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16. Additional file 2 of Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at

Author

Muntau, Ania C., Burlina, Alberto, Eyskens, François, Freisinger, Peter, Leuzzi, Vincenzo, Sivri, Hatice Serap, Gramer, Gwendolyn, Pazdírková, Renata, Cleary, Maureen, Lotz-Havla, Amelia S., Lane, Paul, Alvarez, Ignacio, and Rutsch, Frank

Abstract

Additional file 2: Table S2. Blood Phe levels in patients with treatment-emergent hypophenylalaninaemia.

Published
2021
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17. Additional file 1 of Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at

Author

Muntau, Ania C., Burlina, Alberto, Eyskens, François, Freisinger, Peter, Leuzzi, Vincenzo, Sivri, Hatice Serap, Gramer, Gwendolyn, Pazdírková, Renata, Cleary, Maureen, Lotz-Havla, Amelia S., Lane, Paul, Alvarez, Ignacio, and Rutsch, Frank

Abstract

Additional file 1: Table S1. Status at the end of the extension period—ITTE population.

Published
2021
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18. Additional file 1 of Impact of long-term elosulfase alfa treatment on clinical and patient-reported outcomes in patients with mucopolysaccharidosis type IVA: results from a Managed Access Agreement in England

Author

Cleary, Maureen, Davison, James, Gould, Rachel, Tarekegn Geberhiwot, Derralynn Hughes, Mercer, Jean, Morrison, Alexandra, Murphy, Elaine, Saikat Santra, Jarrett, James, Mukherjee, Swati, and Stepien, Karolina M.

Subjects
human activities
Abstract

Additional file 1: Table S1. Exclusion and starting criteria of the MAA. Table S2. Overview of assessments in the MAA. Figure S1. Flow chart of patient disposition. Figure S2. Urinary keratan sulfate (uKS) over time by age at treatment initiation. Error bars are standard error. Figure S3. Weight over time by age at treatment initiation. Error bars are standard error. Figure S4. 6-minute walk test (6MWT) distance outcomes over time for patients from MOR-002 compared to natural history data from MOR-001 (MOR-001 data linearly extrapolated beyond year 2). Error bars are standard error. Figure S5. 6-minute walk test (6MWT) distance over time by age at treatment initiation compared to results from untreated patients from the MOR-001 natural history study (MOR-001 data linearly extrapolated beyond year 2). Error bars are standard error. Figure S6. Change in FVC (A) and FEV1 (B) over time by age group with comparison to MOR-001 natural history (MOR-001 data available for FVC only, linearly extrapolated beyond year 2). Error bars are standard error. Figure S7. Changes in pulmonary function from baseline to last follow-up (N = 40). Decline: ≥ 0.1 L decrease; Improvement: ≥ 0.1 L increase; Stability

Published
2021
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19. Long-term cognitive and psychosocial outcomes in adults with phenylketonuria

Author

Aitkenhead, Lynne, Krishna, Gauri, Ellerton, Charlotte, Moinuddin, Md, Matcham, Jessica, Shiel, Lisha, Hossain, Shasoty, Kiffin, Marianne, Foley, Jennifer, Skeath, Rachel, Cleary, Maureen, Lachmann, Robin, Murphy, Elaine, Aitkenhead, Lynne, Krishna, Gauri, Ellerton, Charlotte, Moinuddin, Md, Matcham, Jessica, Shiel, Lisha, Hossain, Shasoty, Kiffin, Marianne, Foley, Jennifer, Skeath, Rachel, Cleary, Maureen, Lachmann, Robin, and Murphy, Elaine

Abstract

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. 154 participants underwent cognitive testing, assessing attention, learning, working memory, language, executive functioning and processing speed. 149 completed measures of psychosocial functioning, documenting educational, occupational, quality of life, emotional and social outcomes which were compared with a group of healthy controls. Many adults with PKU demonstrated cognitive impairments, most frequently affecting processing speed (23%), executive function (20%) and learning (12%). Cognitive outcomes were related to measures of historic metabolic control, but only processing speed was significantly related to phenylalanine concentration at the time of testing after controlling for historic levels. Adults with PKU did not, however, differ from controls in educational, occupational, quality of life or emotional outcomes, or on a measure of family functioning, and showed only minor differences in relationship style. These findings have implications for patient counselling and decisions regarding the management of PKU in adulthood. This article is protected by copyright. All rights reserved.

Published
2021

20. Diagnosing Mitochondrial Disorders Remains Challenging in the Omics Era

Author

Forny, Patrick, primary, Footitt, Emma, additional, Davison, James E., additional, Lam, Amanda, additional, Woodward, Cathy E., additional, Batzios, Spyros, additional, Bhate, Sanjay, additional, Chakrapani, Anupam, additional, Cleary, Maureen, additional, Gissen, Paul, additional, Grunewald, Stephanie, additional, Hurst, Jane A., additional, Scott, Richard, additional, Heales, Simon, additional, Jacques, Thomas S., additional, Cullup, Thomas, additional, and Rahman, Shamima, additional

Published
2021
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21. Clinical Genetics of Prolidase Deficiency: An Updated Review

Author

Spodenkiewicz, Marta, Spodenkiewicz, Michel, Cleary, Maureen, Massier, Marie, Fitsialos, Giorgos, Cottin, Vincent, Jouret, Guillaume, Poirsier, Céline, Doco-Fenzy, Martine, Lèbre, Anne-Sophie, SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Equipe OUTRE-MER (IPSOM) (U1178 Inserm), Santé mentale et santé publique (SMSP - U1178), and Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
lcsh:Biology (General), systematic review, PEPD gene, [SDV]Life Sciences [q-bio], prolidase deficiency, Review, lcsh:QH301-705.5
Abstract

International audience; Prolidase is a ubiquitous enzyme that plays a major role in the metabolism of proline-rich proteins. Prolidase deficiency is a rare autosomal recessive inborn metabolic and multisystemic disease, characterized by a protean association of symptoms, namely intellectual disability, recurrent infections, splenomegaly, skin lesions, auto-immune disorders and cytopenia. To our knowledge, no published review has assembled the different clinical data and research studies over prolidase deficiency. The aim of this study is to summarize the actual state of the art from the descriptions of all the patients with a molecular diagnosis of prolidase deficiency reported to date regarding the clinical, biological, histopathological features, therapeutic options and functional studies.

Published
2020

22. Bayesian Inference Associates Rare KDR Variants With Specific Phenotypes in Pulmonary Arterial Hypertension

Author

Swietlik, Emilia M., primary, Greene, Daniel, additional, Zhu, Na, additional, Megy, Karyn, additional, Cogliano, Marcella, additional, Rajaram, Smitha, additional, Pandya, Divya, additional, Tilly, Tobias, additional, Lutz, Katie A., additional, Welch, Carrie C.L., additional, Pauciulo, Michael W., additional, Southgate, Laura, additional, Martin, Jennifer M., additional, Treacy, Carmen M., additional, Penkett, Christopher J., additional, Stephens, Jonathan C., additional, Bogaard, Harm J., additional, Church, Colin, additional, Coghlan, Gerry, additional, Coleman, Anna W., additional, Condliffe, Robin, additional, Eichstaedt, Christina A., additional, Eyries, Mélanie, additional, Gall, Henning, additional, Ghio, Stefano, additional, Girerd, Barbara, additional, Grünig, Ekkehard, additional, Holden, Simon, additional, Howard, Luke, additional, Humbert, Marc, additional, Kiely, David G., additional, Kovacs, Gabor, additional, Lordan, Jim, additional, Machado, Rajiv D., additional, MacKenzie Ross, Robert V., additional, McCabe, Colm, additional, Moledina, Shahin, additional, Montani, David, additional, Olschewski, Horst, additional, Pepke-Zaba, Joanna, additional, Price, Laura, additional, Rhodes, Christopher J., additional, Seeger, Werner, additional, Soubrier, Florent, additional, Suntharalingam, Jay, additional, Toshner, Mark R., additional, Vonk Noordegraaf, Anton, additional, Wharton, John, additional, Wild, James M., additional, Wort, Stephen John, additional, Lawrie, Allan, additional, Wilkins, Martin R., additional, Trembath, Richard C., additional, Shen, Yufeng, additional, Chung, Wendy K., additional, Swift, Andrew J., additional, Nichols, William C., additional, Morrell, Nicholas W., additional, Gräf, Stefan, additional, Abbs, Stephen, additional, Abulhoul, Lara, additional, Adlard, Julian, additional, Ahmed, Munaza, additional, Aitman, Timothy J., additional, Alachkar, Hana, additional, Allsup, David J., additional, Ancliff, Philip, additional, Antrobus, Richard, additional, Armstrong, Ruth, additional, Arno, Gavin, additional, Ashford, Sofie, additional, Astle, William J., additional, Attwood, Anthony, additional, Aurora, Paul, additional, Babbs, Christian, additional, Bacchelli, Chiara, additional, Bakchoul, Tamam, additional, Banka, Siddharth, additional, Bariana, Tadbir, additional, Barwell, Julian, additional, Batista, Joana, additional, Baxendale, Helen E., additional, Beales, Phil L., additional, Bennett, David L., additional, Bierzynska, Agnieszka, additional, Biss, Tina, additional, Bitner-Glindzicz, Maria A.K., additional, Black, Graeme C., additional, Bleda, Marta, additional, Blesneac, Iulia, additional, Bockenhauer, Detlef, additional, Boyce, Sara, additional, Bradley, John R., additional, Breen, Gerome, additional, Brennan, Paul, additional, Brewer, Carole, additional, Brown, Matthew, additional, Browning, Andrew C., additional, Browning, Michael J., additional, Buchan, Rachel J., additional, Buckland, Matthew S., additional, Bueser, Teofila, additional, Diz, Carmen Bugarin, additional, Burn, John, additional, Burns, Siobhan O., additional, Burren, Oliver S., additional, Burrows, Nigel, additional, Campbell, Carolyn, additional, Carr-White, Gerald, additional, Carss, Keren, additional, Casey, Ruth, additional, Caulfield, Mark J., additional, Chambers, Jenny, additional, Chambers, John, additional, Chan, Melanie M.Y., additional, Cheng, Floria, additional, Chinnery, Patrick F., additional, Chitre, Manali, additional, Christian, Martin T., additional, Clayton-Smith, Jill, additional, Cleary, Maureen, additional, Brod, Naomi Clements, additional, Colby, Elizabeth, additional, Cole, Trevor R.P., additional, Collins, Janine, additional, Collins, Peter W., additional, Compton, Cecilia J., additional, Cook, H. Terence, additional, Cook, Stuart, additional, Cooper, Nichola, additional, Corris, Paul A., additional, Curry, Nicola S., additional, Daniels, Matthew J., additional, Dattani, Mehul, additional, Daugherty, Louise C., additional, Davis, John, additional, De Soyza, Anthony, additional, Deevi, Sri V.V., additional, Dent, Timothy, additional, Deshpande, Charu, additional, Dewhurst, Eleanor F., additional, Dixon, Peter H., additional, Douzgou, Sofia, additional, Downes, Kate, additional, Drazyk, Anna M., additional, Drewe, Elizabeth, additional, Duarte, Daniel, additional, Dutt, Tina, additional, Edgar, J. David M., additional, Edwards, Karen, additional, Egner, William, additional, Ekani, Melanie N., additional, Elliott, Perry, additional, Erber, Wendy N., additional, Erwood, Marie, additional, Estiu, Maria C., additional, Evans, Dafydd Gareth, additional, Evans, Gillian, additional, Everington, Tamara, additional, Fassihi, Hiva, additional, Favier, Remi, additional, Fletcher, Debra, additional, Flinter, Frances A., additional, Floto, R. Andres, additional, Fowler, Tom, additional, Fox, James, additional, Frary, Amy J., additional, French, Courtney E., additional, Freson, Kathleen, additional, Frontini, Mattia, additional, Furnell, Abigail, additional, Gale, Daniel P., additional, Ganesan, Vijeya, additional, Gattens, Michael, additional, Ghofrani, Hossein-Ardeschir, additional, Gibbs, J. Simon R., additional, Gibson, Kate, additional, Gilmour, Kimberly C., additional, Gleadall, Nicholas S., additional, Goddard, Sarah, additional, Gomez, Keith, additional, Gordins, Pavels, additional, Gosal, David, additional, Graham, Jodie, additional, Grassi, Luigi, additional, Greenhalgh, Lynn, additional, Greinacher, Andreas, additional, Gresele, Paolo, additional, Griffiths, Philip, additional, Grigoriadou, Sofia, additional, Grozeva, Detelina, additional, Gurnell, Mark, additional, Hackett, Scott, additional, Hadinnapola, Charaka, additional, Hague, Rosie, additional, Hague, William M., additional, Haimel, Matthias, additional, Hall, Matthew, additional, Hanson, Helen L., additional, Haque, Eshika, additional, Harkness, Kirsty, additional, Harper, Andrew R., additional, Harris, Claire L., additional, Hart, Daniel, additional, Hassan, Ahamad, additional, Hayman, Grant, additional, Henderson, Alex, additional, Herwadkar, Archana, additional, Hoffman, Jonathan, additional, Horvath, Rita, additional, Houlden, Henry, additional, Houweling, Arjan C., additional, Hu, Fengyuan, additional, Hudson, Gavin, additional, Huissoon, Aarnoud P., additional, Hurles, Matthew, additional, Irving, Melita, additional, Izatt, Louise, additional, James, Roger, additional, Johnson, Sally A., additional, Jolles, Stephen, additional, Jolley, Jennifer, additional, Josifova, Dragana, additional, Jurkute, Neringa, additional, Kasanicki, Mary A., additional, Kazkaz, Hanadi, additional, Kazmi, Rashid, additional, Kelleher, Peter, additional, Kelly, Anne M, additional, Kelsall, Wilf, additional, Kempster, Carly, additional, Kingston, Nathalie, additional, Koelling, Nils, additional, Kostadima, Myrto, additional, Koziell, Ania, additional, Kreuzhuber, Roman, additional, Kuijpers, Taco W., additional, Kumar, Ajith, additional, Kumararatne, Dinakantha, additional, Kurian, Manju A., additional, Laffan, Michael A., additional, Lalloo, Fiona, additional, Lambert, Michele, additional, Allen, Hana Lango, additional, Layton, D. Mark, additional, Lentaigne, Claire, additional, Lester, Tracy, additional, Levine, Adam P., additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena E., additional, Louka, Eleni, additional, Lyons, Paul A., additional, Madan, Bella, additional, Maher, Eamonn R., additional, Maimaris, Jesmeen, additional, Malka, Samantha, additional, Mangles, Sarah, additional, Mapeta, Rutendo, additional, Marchbank, Kevin J., additional, Marks, Stephen, additional, Markus, Hugh S., additional, Marschall, Hanns-Ulrich, additional, Marshall, Andrew, additional, Mathias, Mary, additional, Matthews, Emma, additional, Maxwell, Heather, additional, McAlinden, Paul, additional, McCarthy, Mark I., additional, McKinney, Harriet, additional, Meacham, Stuart, additional, Mead, Adam J., additional, Mehta, Sarju G., additional, Michaelides, Michel, additional, Millar, Carolyn, additional, Mohammed, Shehla N., additional, Moore, Anthony T., additional, Mozere, Monika, additional, Muir, Keith W., additional, Mumford, Andrew D., additional, Nemeth, Andrea H., additional, Newman, William G., additional, Newnham, Michael, additional, Noorani, Sadia, additional, Nurden, Paquita, additional, O’Sullivan, Jennifer, additional, Obaji, Samya, additional, Odhams, Chris, additional, Okoli, Steven, additional, Olschewski, Andrea, additional, Ong, Kai Ren, additional, Oram, S. Helen, additional, Ormondroyd, Elizabeth, additional, Ouwehand, Willem H., additional, Palles, Claire, additional, Papadia, Sofia, additional, Park, Soo-Mi, additional, Parry, David, additional, Patel, Smita, additional, Paterson, Joan, additional, Peacock, Andrew, additional, Pearce, Simon H., additional, Peerlinck, Kathelijne, additional, Petersen, Romina, additional, Pilkington, Clarissa, additional, Poole, Kenneth E.S., additional, Psaila, Bethan, additional, Pyle, Angela, additional, Quinton, Richard, additional, Rahman, Shamima, additional, Rao, Anupama, additional, Raymond, F. Lucy, additional, Rayner-Matthews, Paula J., additional, Rendon, Augusto, additional, Renton, Tara, additional, Rice, Andrew S.C., additional, Richter, Alex, additional, Robert, Leema, additional, Roberts, Irene, additional, Rose, Sarah J., additional, Ross-Russell, Robert, additional, Roughley, Catherine, additional, Roy, Noemi B.A., additional, Ruddy, Deborah M., additional, Sadeghi-Alavijeh, Omid, additional, Saleem, Moin A., additional, Samani, Nilesh, additional, Samarghitean, Crina, additional, Sanchis-Juan, Alba, additional, Sargur, Ravishankar B., additional, Sarkany, Robert N., additional, Satchell, Simon, additional, Savic, Sinisa, additional, Sayer, Genevieve, additional, Sayer, John A., additional, Scelsi, Laura, additional, Schaefer, Andrew M., additional, Schulman, Sol, additional, Scott, Richard, additional, Scully, Marie, additional, Searle, Claire, additional, Sen, Arjune, additional, Sewell, W.A. Carrock, additional, Seyres, Denis, additional, Shah, Neil, additional, Shamardina, Olga, additional, Shapiro, Susan E., additional, Shaw, Adam C., additional, Sibson, Keith, additional, Side, Lucy, additional, Simeoni, Ilenia, additional, Simpson, Michael A., additional, Sims, Matthew C., additional, Sivapalaratnam, Suthesh, additional, Smedley, Damian, additional, Smith, Katherine R., additional, Smith, Kenneth G.C., additional, Snape, Katie, additional, Soranzo, Nicole, additional, Spasic-Boskovic, Olivera, additional, Staines, Simon, additional, Staples, Emily, additional, Stark, Hannah, additional, Stirrups, Kathleen E., additional, Stuckey, Alex, additional, Syrris, Petros, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Tan, Rhea Y.Y., additional, Taylor, Jenny C., additional, Taylor, John M., additional, Thaventhiran, James E., additional, Themistocleous, Andreas C., additional, Thomas, David, additional, Thomas, Ellen, additional, Thomas, Moira J., additional, Thomas, Patrick, additional, Thomson, Kate, additional, Thrasher, Adrian J., additional, Thys, Chantal, additional, Tischkowitz, Marc, additional, Titterton, Catherine, additional, Toh, Cheng-Hock, additional, Tomlinson, Ian P., additional, Traylor, Matthew, additional, Treadaway, Paul, additional, Tuna, Salih, additional, Turro, Ernest, additional, Twiss, Philip, additional, Vale, Tom, additional, Van Geet, Chris, additional, van Zuydam, Natalie, additional, Vandersteen, Anthony M, additional, Vazquez-Lopez, Marta, additional, von Ziegenweidt, Julie, additional, Wagner, Annette, additional, Waisfisz, Quinten, additional, Walker, Neil, additional, Walker, Suellen M., additional, Ware, James S., additional, Watkins, Hugh, additional, Watt, Christopher, additional, Webster, Andrew R., additional, Wedderburn, Lucy, additional, Wei, Wei, additional, Welch, Steven B., additional, Wessels, Julie, additional, Westbury, Sarah K., additional, Westwood, John-Paul, additional, Whitehorn, Deborah, additional, Whitworth, James, additional, Wilkie, Andrew O.M., additional, Williamson, Catherine, additional, Wilson, Brian T., additional, Wong, Edwin K.S., additional, Wood, Nicholas, additional, Wood, Yvette, additional, Woods, Christopher Geoffrey, additional, Woodward, Emma R., additional, Worth, Austen, additional, Wright, Michael, additional, Yates, Katherine, additional, Yong, Patrick F.K., additional, Young, Timothy, additional, Yu, Ping, additional, Yu-Wai-Man, Patrick, additional, Zlamalova, Eliska, additional, Hirsch, Russel, additional, White, R. James, additional, Simon, Marc, additional, Badesch, David, additional, Rosenzweig, Erika, additional, Burger, Charles, additional, Chakinala, Murali, additional, Thenappan, Thenappan, additional, Elliott, Greg, additional, Simms, Robert, additional, Farber, Harrison, additional, Frantz, Robert, additional, Elwing, Jean, additional, Hill, Nicholas, additional, Ivy, Dunbar, additional, Klinger, James, additional, Nathan, Steven, additional, Oudiz, Ronald, additional, Robbins, Ivan, additional, Schilz, Robert, additional, Fortin, Terry, additional, Wilt, Jeffrey, additional, Yung, Delphine, additional, Austin, Eric, additional, Ahmad, Ferhaan, additional, Bhatt, Nitin, additional, Lahm, Tim, additional, Frost, Adaani, additional, Safdar, Zeenat, additional, Rehman, Zia, additional, Walter, Robert, additional, Torres, Fernando, additional, Bakshi, Sahil, additional, Archer, Stephen, additional, Argula, Rahul, additional, Barnett, Christopher, additional, Benza, Raymond, additional, Desai, Ankit, additional, and Maddipati, Veeranna, additional

Published
2021
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27. Genetic counseling and prenatal diagnosis for the mitochondrial DNA mutations at nucleotide 8993

Author

White, Sarah L., Collins, Veronica R., Wolfe, Rory, Cleary, Maureen A., Shanske, Sara, DiMauro, Salvatore, Dahl, Hans-Henrik M., and Thorburn, David R.

Subjects
Genetic disorders -- Diagnosis, Chromosome mapping -- Usage, Mitochondrial DNA -- Diagnosis, Genetic counseling -- Usage, Biological sciences
Abstract

Prenatal diagnosis for the mitochondrial nucleotide 8993 DNA mutations is discussed as it relates to genetic counseling and data from 56 pedigrees used to find empirical recurrence risks. Heteroplasmy, or mutant load, which can vary from 1-99%, complicates mitochondrial genetics and makes it difficult to predict clinical severity to be expected from mutant load measured in fetal tissue.

Published
1999

28. Urea Cycle Related Amino Acids Measured in Dried Bloodspots Enable Long-Term In Vivo Monitoring and Therapeutic Adjustment

Author

Baruteau, Julien, primary, Khalil, Youssef, additional, Grunewald, Stephanie, additional, Zancolli, Marta, additional, Chakrapani, Anupam, additional, Cleary, Maureen, additional, Davison, James, additional, Footitt, Emma, additional, Waddington, Simon N., additional, Gissen, Paul, additional, and Mills, Philippa, additional

Published
2019
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30. Additional file 1: Figure S1. of Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial

Author

Muntau, Ania, Burlina, Alberto, Eyskens, François, Freisinger, Peter, Laet, Corinne De, Leuzzi, Vincenzo, Rutsch, Frank, H. Sivri, Vijay, Suresh, Bal, Milva, Gramer, Gwendolyn, Pazdírková, Renata, Cleary, Maureen, Lotz-Havla, Amelie, Munafo, Alain, Mould, Diane, Moreau-Stucker, Flavie, and Rogoff, Daniela

Abstract

Summary of neuromotor developmental milestones – ITT population. Data show (a) the proportion of patients with normal development in the area of assessment at baseline, (b) Week 12, and (c) Week 26 treated with sapropterin plus the Phe-restricted diet, or Phe-restricted diet alone. P-values show comparison of results between treatment groups at Week 26 using the chi-squared test. Table S1. PAH genotypes of sapropterin responders (n=37). (DOCX 180 kb)

Published
2017
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33. Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial

Author

Muntau, Ania Carolina, Bal, Milva Orquidea, Gramer, Gwendolyn, Pazdírková, Renata, Cleary, Maureen Anne M., Lotz-Havla, Amelie Sophia, Munafo, Alain, Mould, Diane D.R., Moreau-Stucker, Flavie, Rogoff, Daniela, Burlina, Alberto, Eyskens, François J M F., Freisinger, Peter, De Laet, Corinne, Leuzzi, Vincenzo, Rutsch, Frank, Sivri, Hatice Serap, Vijay, Suresh, Muntau, Ania Carolina, Bal, Milva Orquidea, Gramer, Gwendolyn, Pazdírková, Renata, Cleary, Maureen Anne M., Lotz-Havla, Amelie Sophia, Munafo, Alain, Mould, Diane D.R., Moreau-Stucker, Flavie, Rogoff, Daniela, Burlina, Alberto, Eyskens, François J M F., Freisinger, Peter, De Laet, Corinne, Leuzzi, Vincenzo, Rutsch, Frank, Sivri, Hatice Serap, and Vijay, Suresh

Abstract

Background: Sapropterin dihydrochloride, a synthetic formulation of BH4, the cofactor for phenylalanine hydroxylase (PAH, EC 1.14.16.1), was initially approved in Europe only for patients ≥4 years with BH4-responsive phenylketonuria. The aim of the SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) trial was to assess the efficacy (improvement in daily phenylalanine tolerance, neuromotor development and growth parameters), safety and pharmacokinetics of sapropterin dihydrochloride in children <4 years. Results: In total, 109 male or female children <4 years with confirmed BH4-responsive phenylketonuria or mild hyperphenylalaninemia and good adherence to dietary treatment were screened. 56 patients were randomly assigned (1:1) to 10 mg/kg/day oral sapropterin plus a phenylalanine-restricted diet or to only a phenylalanine-restricted diet for 26 weeks (27 to the sapropterin and diet group and 29 to the diet-only group; intention-to-treat population). Of these, 52 patients with ≥1 pharmacokinetic sample were included in the pharmacokinetic analysis, and 54 patients were included in the safety analysis. At week 26 in the sapropterin plus diet group, mean phenylalanine tolerance was 30.5 (95% confidence interval 18.7-42.3) mg/kg/day higher than in the diet-only group (p < 0.001). The safety profile of sapropterin, measured monthly, was acceptable and consistent with that seen in studies of older children. Using non-linear mixed effect modelling, a one-compartment model with flip-flop pharmacokinetic behaviour, in which the effect of weight was substantial, best described the pharmacokinetic profile. Patients in both groups had normal neuromotor development and stable growth parameters. Conclusions: The addition of sapropterin to a phenylalanine-restricted diet was well tolerated and led to a significant improvement in phenylalanine tolerance in children <4 years with BH4-responsive phenylketonuria or mild hyperphenylalaninemia. The pharmacokinetic model favou, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

34. Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III

Author

Ghosh, Arunabha, primary, Shapiro, Elsa, additional, Rust, Stewart, additional, Delaney, Kathleen, additional, Parker, Samantha, additional, Shaywitz, Adam J, additional, Morte, Adelaida, additional, Bubb, Gillian, additional, Cleary, Maureen, additional, Bo, Tien, additional, Lavery, Christine, additional, Bigger, Brian W, additional, and Jones, Simon A, additional

Published
2017
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35. Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial

Author

Muntau, Ania C., primary, Burlina, Alberto, additional, Eyskens, François, additional, Freisinger, Peter, additional, De Laet, Corinne, additional, Leuzzi, Vincenzo, additional, Rutsch, Frank, additional, Sivri, H. Serap, additional, Vijay, Suresh, additional, Bal, Milva Orquidea, additional, Gramer, Gwendolyn, additional, Pazdírková, Renata, additional, Cleary, Maureen, additional, Lotz-Havla, Amelie S., additional, Munafo, Alain, additional, Mould, Diane R., additional, Moreau-Stucker, Flavie, additional, and Rogoff, Daniela, additional

Published
2017
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36. Diagnostic and management practices for phenylketonuria in 19 countries of the South and Eastern European Region: survey results

Author

Giżewska, Maria, MacDonald, Anita, Bélanger-Quintana, Amaya, Burlina, Alberto, Cleary, Maureen, Coşkun, Turgay, Feillet, François, Muntau, Ania C, Trefz, Friedrich K, van Spronsen, Francjan J, Blau, Nenad, Giżewska, Maria, MacDonald, Anita, Bélanger-Quintana, Amaya, Burlina, Alberto, Cleary, Maureen, Coşkun, Turgay, Feillet, François, Muntau, Ania C, Trefz, Friedrich K, van Spronsen, Francjan J, and Blau, Nenad

Abstract

To avoid potentially severe outcomes, phenylketonuria (PKU) must be detected as soon as possible after birth and managed with life-long treatment. A questionnaire-based survey was performed to document diagnosis and management practices for PKU in a region of Southern and Eastern Europe. Prevalence and management data were obtained from 37/59 (63 %) centres within 19/22 (86%) contacted countries (N = 8600 patients). The main results' analysis was based on completed questionnaires obtained from 31 centres (53%) within 15 countries (68%). A median of 10 % of patients per centre had been diagnosed after the newborn period. Metabolic dieticians and specialised adult PKU clinics were lacking in 36 and 84% of centres, respectively. In 26% of centres, treatment initiation was delayed until >15 days of life. Blood phenylalanine (Phe) thresholds to start treatment and upper Phe targets were inconsistent across centres. Ten percent of centres reported monitoring Phe every 2 weeks for pregnant women with PKU, which is insufficient to minimise risk of neonatal sequalae. Sapropterin dihydrochloride treatment was available in 48% of centres, with 24-h responsiveness tests most common (36%). Only one centre among the five countries lacking newborn screening provided a completed questionnaire. CONCLUSION: Targeted efforts by health care professionals and governments are needed to optimise diagnostic and management approaches for PKU in Southern and Eastern Europe. WHAT IS KNOWN: PKU must be detected early and optimally managed throughout life to avoid poor outcomes, yet newborn screening is not universal and diagnostic and management practices for PKU are known to vary widely between different centres and countries. Targeted efforts by health care professionals and governments are needed to optimise diagnostic and management approaches. WHAT IS NEW: PKU management practices are documented in 19 South and Eastern European countries indicating a heterogeneous situation across the reg

Published
2016

37. Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes

Author

Reid, Emma S., primary, Papandreou, Apostolos, additional, Drury, Suzanne, additional, Boustred, Christopher, additional, Yue, Wyatt W., additional, Wedatilake, Yehani, additional, Beesley, Clare, additional, Jacques, Thomas S., additional, Anderson, Glenn, additional, Abulhoul, Lara, additional, Broomfield, Alex, additional, Cleary, Maureen, additional, Grunewald, Stephanie, additional, Varadkar, Sophia M., additional, Lench, Nick, additional, Rahman, Shamima, additional, Gissen, Paul, additional, Clayton, Peter T., additional, and Mills, Philippa B., additional

Published
2016
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39. Erratum: CORRIGENDUM: Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome

Author

Muenzer, Joseph, primary, Beck, Michael, additional, Eng, Christine M, additional, Giugliani, Roberto, additional, Harmatz, Paul, additional, Martin, Rick, additional, Ramaswami, Uma, additional, Vellodi, Ashok, additional, Wraith, James E, additional, Cleary, Maureen, additional, Gucsavas-Calikoglu, Muge, additional, Puga, Ana Cristina, additional, Shinawi, Marwan, additional, Ulbrich, Birgit, additional, Vijayaraghavan, Suresh, additional, Wendt, Susanne, additional, Conway, Anne Marie, additional, Rossi, Alexandra, additional, Whiteman, David A H, additional, and Kimura, Alan, additional

Published
2013
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40. DRIVING WITH DEMENTIA: THE NECESSITY OF A COMPREHENSIVE REPORTING SCHEME.

Author

Cleary, Maureen

Subjects
DEMENTIA, DRIVERS' licenses, SELF-reliance
Abstract

More than simply a rite of passage, obtaining a driver's license is an imperative step in asserting one's independence and self-reliance. However, as drivers age an their physical and mental capabilities begin to decline, many families and caregiver for the elderly are faced with the difficult choice of restricting driving privileges. The lack of a uniform rule on when an elderly person is no longer capable of driving, as well as who should make that decision and on what basis, has fostered only confusion and resentment. The uncertainty is only exacerbated by the numerous and often well-publicized incidents of deadly accidents involving elderly drivers. Fairness to our seniors and our society demands decisive action on this complex issue. This Note recommends comprehensive reform nationally to state licensing practices, as well as physician reporting requirements, to adopt a uniform system of elderly driver evaluation. First, analyzing the shortfalls of the current system, this Note then illustrates how this far-reaching reform balances both the independence of seniors and the interests of society. Following the diagnosis and mandatory reporting of certain cognitive impairments, state driving facilities will employ driving rehabilitation specialists to thoroughly assess driving capabilities and impose any applicable restriction. Individualized evaluation based on standardized criteria respects both the needs of elders and the safety of the public. [ABSTRACT FROM AUTHOR]

Published
2016

41. Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome

Author

Muenzer, Joseph, primary, Beck, Michael, additional, Eng, Christine M., additional, Giugliani, Roberto, additional, Harmatz, Paul, additional, Martin, Rick, additional, Ramaswami, Uma, additional, Vellodi, Ashok, additional, Wraith, James E., additional, Cleary, Maureen, additional, Gucsavas-Calikoglu, Muge, additional, Puga, Ana Cristina, additional, Shinawi, Marwan, additional, Ulbrich, Birgit, additional, Vijayaraghavan, Suresh, additional, Wendt, Susanne, additional, Conway, Anne Marie, additional, Rossi, Alexandra, additional, Whiteman, David A.H., additional, and Kimura, Alan, additional

Published
2011
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43. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Author

Muenzer, Joseph, primary, Wraith, James E., additional, Beck, Michael, additional, Giugliani, Roberto, additional, Harmatz, Paul, additional, Eng, Christine M., additional, Vellodi, Ashok, additional, Martin, Rick, additional, Ramaswami, Uma, additional, Gucsavas-Calikoglu, Muge, additional, Vijayaraghavan, Suresh, additional, Wendt, Suzanne, additional, Puga, Antonio, additional, Ulbrich, Brian, additional, Shinawi, Marwan, additional, Cleary, Maureen, additional, Piper, Diane, additional, Conway, Ann Marie, additional, and Kimura, Alan, additional

Published
2006
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44. Adamstown

Author

Adamstown, Cuirtéis, Donnchadh, Brien, Michael O', Cleary, Maureen, Martin, Micheal, Crean, Nellie, Doyle, Annie, Bradley, Kitty, Cleary, Richard, Doyle, Thomas P., Kelly, Mary B., Murphy, Alice, Gee, Peggie Mc, Lalor, Aidan, Brown, Patrick, Murphy, Maureen, Martin, Michael, Cleary, Richie, Browne, Paddy, and Hughes, Mary L.

Subjects
Folk poetry, Schools, local legends, Legal status, laws, etc, Leprechauns, Agriculture, Supernatural beings, Manners and customs, Death, Ringforts, Food, Riddles, Land use, Dissenters, Religious, Animals, Wake services, Cemeteries, Occupations, Weather, Folklore, Jokes, Treasure troves, Evil eye
Abstract

A collection of folklore and local history stories from Adamstown (school) (Adamstown, Co. Wexford), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Donnchadh Cuirtéis., Ballad - The Ballyshannon Lane / Brien, Michael O' -- Adamstown Races -- Ballad -- Stories / Cleary, Maureen -- There was a man coming home from Adamstown (Co Wexford Bantry) one night about a hundred years ago, and he was a bit boosey. / Martin, Micheal -- A long time ago a man died in Hayestown (Taghmon, Co Wexford, Bantry) sitting up in his bed. / Martin, Micheal -- There was an old woman named Mrs Kelly who lived in Adamstown, Bantry, Co Wexford. / Crean, Nellie -- There was a certain man one time who lived in Galbally. / Doyle, Annie -- There was a man one time and his name was Nolan. / Bradley, Kitty -- Two young men went to a dance one night. / Cleary, Maureen -- One day about twenty years ago, I went to my uncle's house, with an ass to get a car. / Cleary, Richard -- About thirty years ago a young man was going to the fair, and before he started from home he went to the well. / Cleary, Richard -- There was a girl by the name of Catherine Reddy. / Doyle, Thomas P. -- In olden times there did only two Catholics families live in the town of Old Ross (Ballinaboola Co Wexford). All the rest of the people were called Palentines. / Doyle, Thomas P. -- In the sixties of the last century there lived a small farmer in Misterin (Adamstown Co Wexford) named Pat Bradey. / Doyle, Thomas P. -- Some years ago a man by the name of Jones had a tan-yard in New Ross (Co Wexford Barony of Bantry). / Doyle, Thomas P. -- Long ago an old tinker by the name of Tom Swaine used to go around Adamstown mending things at houses. / Kelly, Mary B. -- I was out rambling and begod it was late and I coming home. / Murphy, Alice -- About a century ago, there was a bonfire at Nash, Newbawn, Co Wexford, Barony of Shelbourne. / Gee, Peggie Mc -- A crowd of young men went to hunt one day, and it was getting dark when they went to an old castle to dig for a badger. / Cleary, Maureen -- A man named Micheal Hayes was coming home from a neighbour's house one night. / Kelly, Mary B. -- Once upon a time there was an old rath in which there used to be fairies. / Bradley, Kitty -- There was a light seen in Mr John O'Gorman's field nearly every night. / Crean, Nellie -- About a hundred years ago two fellas used to be in the habit of rambling to a certain house in Newtown (Adamstown, Co Wexford). / Martin, Micheal -- There was a wake in Hayestown, Taghmon, Co Wexford, Bantry a very long long time ago. / Martin, Micheal -- One time not very long ago, there lived two ould persons, Dick and Biddy at one side of Taghmon. / Gee, Peggie Mc -- There is an old graveyard on Mr Byrne's land (Doonooney Adamstown, Co Wexford). / Cleary, Maureen -- There is an ould stone in Mary Foley's ditch on the Coolnagree side of the road. / Murphy, Alice -- There was a certain man going home from Adamstown, and he met a girl coming down the Leap road one night. / Murphy, Alice -- There were protestants lived in a house in Ballybrennan where Mr Deacon now lives. / Murphy, Alice -- There is an ould house in Ballybrennan. / Murphy, Alice -- There is a stone standing out of a piece from the ditch in a field in Coolnagree and another stone out on the road. / Murphy, Alice -- There was a man by the name of John Furlong who lived in Scullabogue (Newbawn Co Wexford). / Doyle, Thomas P. -- There was a wake held in an old house one time. / Cleary, Maureen -- Long ago an ould man be the name of Tom Byrne and his wife Biddy lived in Doonooney. / Kelly, Mary B. -- There was a man be the name of Quirke who lived down in Macmine. / Murphy, Alice -- There was often a black dog seen over on a path someplace about Kellystown. / Murphy, Alice -- There was often men with tall red hats seen in Roche's rath Assegart Foulksmills. / Murphy, Alice -- There was a priest one time who lived near Ballymitty. / Murphy, Alice -- There was a man named Pat Chapman of Barmoney coming home late one night. / Murphy, Alice -- There were five fellas going to a dance one night. / Murphy, Alice -- There was a little house in Byrne's castle meadow near where the chapel was in Doonooney. / Murphy, Alice -- An ould fella lived in Taghmon by the name of Jim Keegan the blacksmith. / Martin, Micheal -- Brooms - Food and Trades / Crean, Nellie -- Flails / Martin, Micheal -- Pipes / Murphy, Alice -- Candles / Kelly, Mary B. -- Long ago in my district the people used different food from what they use at present. / Martin, Micheal -- Long ago people made potatoe cakes, barley cakes and oaten cakes, and had them to eat. / Lalor, Aidan -- Candles / Brown, Patrick -- Buried Treasure / Crean, Nellie -- There is an ould rath near our house, and there is said to be money buried in it. / Murphy, Alice -- There is an ould ruined castle situated in Knockreigh, Adamstown. / Crean, Nellie -- Well you asked me for a story; here is one. / Cleary, Maureen -- I am going to tell you a story about some cowards, who went to dig for money in the castle (Traceystown, Taghmon, Co Wexford). / Cleary, Maureen -- In the ould rath that is on this farm, there is a large mound, on which grows blackthorns. / Crean, Nellie -- There is a river called the "Boro" which separates the townslands of Wilton (Bree Co Wexford) and Ballinadara (Davidstown Co Wexford). / Crean, Nellie -- There is an old field situated in Barmoney Bree and it is said that there are two giants buried in this field, and when they were dying they brought their treasures with them. / Doyle, Annie -- I often dug in the ould rath but I never found anything in it. / Murphy, Alice -- There is an ould field in this locality, and there is said to be money buried in it. / Murphy, Alice -- In the year 1798 two Irish soldiers were going to France to join the Irish Brigade. / Gee, Peggie Mc -- There is an old castle at Knockreigh, Adamstown, Barony of Bantry, Co Wexford. / Bradley, Kitty -- Long ago a man named Wat Evoy dreamt three nights after one another, that there was a crock of gold buried in a field of my fathers called the gorteen. / Kelly, Mary B. -- There were two farmers living in Cloughbawn Enniscorthy one time. / Gee, Peggie Mc -- Names of Fields -- Weather-Lore -- Riddles -- Stories / Kelly, Mary B. -- The worst place in Ireland is at Byrne's of Doonooney. / Kelly, Mary B. -- Do you know where the cottage is at the butt of the Hill of Kellystown? / Kelly, Mary B. -- An ould woman lived near Browner's of Camross, Foulksmills, Co Wexford (Bantry). / Kelly, Mary B. -- Ould Jim Cullen and his wife were goin' to town one day and when they were goin' down the hill of Brownstown... / Cleary, Maureen -- Jim Colfer always called his wife "The Madam". / Cleary, Maureen -- There was a poor man with a wife and family. / Cleary, Maureen -- There was an old woman living in Newbawn and she had a son in Kilbarney and he come home to her one day and says he... / Cleary, Maureen -- Folklore / Murphy, Maureen -- There was a man wan time and he went to buy a calf from another man. / Doyle, Annie -- There was a man wan time and he was mowing down a field of hay. / Doyle, Annie -- There was a fella be the name of William Hornick, who lived in Kilgarvan. / Doyle, Annie -- There was a man wan time an' he was lookin' for lodgin' and he got it in a farmer's place. / Doyle, Annie -- Long ago there was a woman, she was very rich, and she had a lot of jewellery an' when she was dying she brought it all wid her. / Doyle, Annie -- Long ago there was a bonfire at Nash an' wan evenin' there were a lot of people dancin' around it. / Doyle, Annie -- There was a man by the name of Paul Roche from Barmoney, Bree, an' he was comin' home from ramblin' wan night. / Doyle, Annie -- One evening as I was comin' home from town, I saw a lepracaun in a marigold field, and just as I was near him, I took my eye off him, an' he disappeared. / Doyle, Annie -- I was pumpin' my bike at the bridge of Scar wan night, an' I heard a big roar, an' I looked around an' I saw a little man about two foot high... / Doyle, Annie -- There was a woman by the name of Biddy Murphy (Faree, Foulksmills, Co Wexford). / Doyle, Thomas P. -- There lived in Rathkyle a very pretty girl named Miss Cox, and there were many who wished to marry her. / Martin, Michael -- Two ould people lived in Coolnagree, be the name of Phil and Mary Jackman. / Martin, Michael -- Some time ago there used to be a black dog seen on the Kellystown road, between Ger Gorman's and the Leap. / Cleary, Richie -- There was a man wan time who was reared as a pet. / Murphy, Maureen -- There wor two men wan time and they stole I think about twelve pounds of mate. / Cleary, Richard -- There was an' ould man an he was supposed to be a brother of this other Quirke fella I have mentioned in the other story. / Murphy, Alice -- Uncle Bob stopped with his aunt in Ballymurren. / Murphy, Alice -- Mesef an' yer father was goin' up the lane wan night a past the ould kiln. / Cleary, Maureen -- Chapel Field / Browne, Paddy -- Sir Richard Devereux (formerly of Carrigmannon, Glynn, Co Wexford) is buried in the old mound in the centre of Adamstown Graveyard. / Hughes, Mary L. -- I was goin up the lane wan night wid the dog. / Cleary, Maureen -- '98 Stories / Cleary, Maureen -- Some time before the Battle of Horetown, in the year of seventeen hundred and ninety eight, there was a young insurgent, who wanted to get a horse. / Cleary, Maureen -- There was an ould woman and her crippled son living alone in Laegawn, Clongeen, Co Wexford where Mr Roche now lives. / Cleary, Maureen -- Shortly after the rebellion of 1798, Michael Dwyer, the Wicklow chieftain, met a representative of the Hume family... / Hughes, Mary L. -- Michael Dwyer's followers about the time of this incident had dwindled down to about a dozen. / Hughes, Mary L. -- There was an ould woman be the name of Kitty Sheekin who lived in Raheenduff (Adamstown Co Wexford). / Hughes, Mary L. -- There was a woman wan time be the name of Mary Evoy who lived in Coonogue (Adamstown, Co Wexford). / Hughes, Mary L. -- One night there was a man be the name of Joseph Doyle comin home from ramblin' from Shelin. / Doyle, Annie -- There was a man be the name of James Kehoe comin' home from ramblin' wan night, an' he saw a light comen through the fields in the distance... / Doyle, Annie, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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45. Detection of neurological abnormalities in adolescents and adults with phenylketonuria

Author

Cleary, Maureen Anne and Cleary, Maureen Anne

Abstract

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt

46. Detection of neurological abnormalities in adolescents and adults with phenylketonuria

Author

Cleary, Maureen Anne and Cleary, Maureen Anne

Abstract

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt

47. Detection of neurological abnormalities in adolescents and adults with phenylketonuria

Author

Cleary, Maureen Anne and Cleary, Maureen Anne

Abstract

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt

48. Detection of neurological abnormalities in adolescents and adults with phenylketonuria

Author

Cleary, Maureen Anne and Cleary, Maureen Anne

Abstract

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt

49. Detection of neurological abnormalities in adolescents and adults with phenylketonuria

Author

Cleary, Maureen Anne and Cleary, Maureen Anne

Abstract

Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt

50. CORRIGENDUM: Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome

Author

Muenzer, Joseph, Beck, Michael, Eng, Christine M, Giugliani, Roberto, Harmatz, Paul, Martin, Rick, Ramaswami, Uma, Vellodi, Ashok, Wraith, James E, Cleary, Maureen, Gucsavas-Calikoglu, Muge, Puga, Ana Cristina, Shinawi, Marwan, Ulbrich, Birgit, Vijayaraghavan, Suresh, Wendt, Susanne, Conway, Anne Marie, Rossi, Alexandra, Whiteman, David A H, and Kimura, Alan

Published
2013
Full Text
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