Article
Health Care Sciences & Services
Min-Sun Kim, Aram Yang, Eu-Seon Noh, Chiwoo Kim, Ga Young Bae, Han Hyuk Lim, Hyung-Doo Park, Sung Yoon Cho, Dong-Kyu Jin
Summary: This study analyzed the genetic and clinical characteristics of MPS III patients in Korea for the first time, revealing the natural history of the disease. The findings contribute to early diagnosis, timely management, and evaluation of treatment outcomes in future clinical trials for MPS III.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Endocrinology & Metabolism
Arunabha Ghosh, Stewart Rust, Kia Langford-Smith, Daniel Weisberg, Maria Canal, Catherine Breen, Michelle Hepburn, Karen Tylee, Frederic M. Vaz, Andy Vail, Frits Wijburg, Claire O'Leary, Helen Parker, J. Ed Wraith, Brian W. Bigger, Simon A. Jones
Summary: This study found that high doses of genistein aglycone therapy did not lead to clinically meaningful reductions in cerebrospinal fluid heparan sulfate concentrations in Sanfilippo syndrome (mucopolysaccharidosis type III), but there was a statistically significant reduction in urinary glycosaminoglycan levels. Other biochemical and clinical parameters showed no significant differences between the two study groups.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Genetics & Heredity
Rutaba Gul, Sabika Firasat, Mikkel Schubert, Asmat Ullah, Elionora Pena, Anne C. B. Thuesen, Mulazim Hussain, Frederik F. Staeger, Anette P. Gjesing, Anders Albrechtsen, Torben Hansen
Summary: The aim of this study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II. Whole genome sequencing revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes, as well as a novel candidate gene for lysosomal storage disorder-like phenotypes. The presence of multigenic inheritance in several families highlights the importance of searching for homozygous pathogenic variants in multiple genes, especially in consanguineous families.
FRONTIERS IN GENETICS
(2023)
Review
Genetics & Heredity
Weijing Kong, Jing Zhang, Cheng Lu, Yingxue Ding, Yan Meng
Summary: Mucopolysaccharidoses are a group of rare lysosomal storage disorders primarily characterized by fatal manifestations. Advances in treatment have led to improved lifespan and quality of life for patients, but abnormal accumulation of glycosaminoglycans in the eye can lead to glaucoma, impacting quality of life and requiring further research.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Erin T. Strovel, Kristina Cusmano-Ozog, Tim Wood, Chunli Yu
Summary: Assays that measure lysosomal enzyme activity are crucial for diagnosing and screening lysosomal storage disorders. This document provides guidance for clinical enzyme testing, including test performance variables and the need for follow-up molecular testing.
GENETICS IN MEDICINE
(2022)
Article
Endocrinology & Metabolism
Yingjun Liang, Xiaolan Gao, Deyun Lu, Huiwen Zhang, Zhang
Summary: This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients from eight families. The mean age at symptom onset was 4.2 years old, and the mean age at diagnosis was 7.6 years old, suggesting a delay in diagnosis. The most common presenting symptoms were speech deterioration, followed by mental deterioration, hyperactivity, and hepatomegaly. All mutant alleles of the patients were identified, including eleven different HGSNAT variants, with the most common one being a previously reported variant.
METABOLIC BRAIN DISEASE
(2023)
Review
Medicine, General & Internal
Sophie Thomas, Uma Ramaswami, Maureen Cleary, Medeah Yaqub, Eva M. Raebel
Summary: MPS III, a rare lysosomal storage disorder, may have GI manifestations as an important cause of death. Early recognition and intervention of GI symptoms are crucial for the management of MPS III patients.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Kohtaro Minami, Hideto Morimoto, Hiroki Morioka, Atsushi Imakiire, Masafumi Kinoshita, Ryuji Yamamoto, Tohru Hirato, Hiroyuki Sonoda
Summary: Heparan sulfate is an important component of proteoglycans and plays a crucial role in various physiological processes. Mutations in genes involved in HS biosynthesis or degradation can lead to diseases, including those affecting the bones and CNS. The accumulation of HS is observed in patients with MPSs, and HS has the potential to be used as a biomarker for disease severity and therapeutic response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Patryk Lipinski, Krzysztof Szczaluba, Piotr Buda, Ekaterina Y. Zakharova, Galina Baydakova, Agnieszka Lugowska, Agnieszka Rozdzynska-Swiatkowska, Zuzanna Cyske, Grzegorz Wegrzyn, Agnieszka Pollak, Rafal Ploski, Anna Tylki-Szymanska
Summary: This article reports a Polish MPS-PS patient with a novel VPS33A gene variant and new clinical features. Functional analysis revealed some related biomarkers, and comparison with other cases helped broaden understanding of the disease phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Antonio Monaco, Alessandro Fraldi
Summary: Mucopolysaccharidoses (MPS) are inherited metabolic diseases with strong neurological involvement. Impairment of autophagy pathway is a key factor driving neurodegeneration in MPS, particularly downstream of the GAG storage.
Article
Biochemistry & Molecular Biology
Nuno Lopes, Maria L. Maia, Catia S. Pereira, Ines Mondragao-Rodrigues, Esmeralda Martins, Rosa Ribeiro, Ana Gaspar, Patricio Aguiar, Paula Garcia, Maria Teresa Cardoso, Esmeralda Rodrigues, Elisa Leao-Teles, Roberto Giugliani, Maria F. F. Coutinho, Sandra Alves, M. Fatima Macedo
Summary: In MPS VI disease patients, there is a decrease in the percentage of natural killer cells and monocytes compared to controls. However, there are no alterations in the percentage of T cells, invariant NKT cells, and B cells in both MPS II and VI disease patients. Interestingly, MPS VI disease patients have a higher frequency of naive T cells and lower memory T cell frequency compared to control subjects.
Article
Genetics & Heredity
Shiri Liber, Orna Staretz-Chacham, Mor Kishon, Ben Pode-Shakked, Odelia Chorin, Katya Kneller, Yair Anikster, Geto Mangisto, Ann Saada, Annick Raas-Rothschild
Summary: Sanfilippo Syndrome is a lysosomal storage disorder caused by enzyme deficiency leading to tissue accumulation of heparan sulfate. It is characterized by progressive neurodegeneration and systemic manifestations. Delayed diagnosis is common, and early clinical features include speech delay, coarse facial features, and global developmental delay.
MOLECULAR SYNDROMOLOGY
(2022)
Article
Oncology
Wei Huang, Yu-Shan Cheng, Shu Yang, Manju Swaroop, Miao Xu, Wenwei Huang, Wei Zheng
Summary: MPS IIIB is a lysosomal disease caused by mutations in the NAGLU gene, with no effective treatment currently available. The study showed that MPS IIIB neural stem cells and neurons can serve as a disease model system for evaluating drug efficacy and compound screening for drug development.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Clinical Neurology
Rita Barone, Agata Fiumara, Mariangela Gulisano, Lara Cirnigliaro, Maria Donatella Cocuzza, Claudia Guida, Fabio Pettinato, Filippo Greco, Maurizio Elia, Renata Rizzo
Summary: MPS III patients often exhibit developmental issues, sleep disturbances, and behavioral abnormalities early in life, with a proportion developing epilepsy. Research indicates that there are patterns in the presentation of epilepsy and EEG changes in MPS III patients.
FRONTIERS IN NEUROLOGY
(2021)
Article
Orthopedics
Sandra Rafaela Breyer, Eik Vettorazzi, Leonie Schmitz, Amit Gulati, Katharina Maria von Cossel, Alexander Spiro, Martin Rupprecht, Ralf Stuecker, Nicole Maria Muschol
Summary: This study revealed a high prevalence of hip pathologies in MPS III patients, with a significant correlation between severe phenotype and hip dysplasia with osteonecrosis of the femoral head. Radiographs of the hips are highly recommended in baseline and follow-up assessments of MPS III patients.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2021)
Article
Genetics & Heredity
Jean-Michel Heard, Charlotte Vrinten, Michael Schlander, Cinzia Maria Bellettato, Corine van Lingen, Maurizio Scarpa, Gert Matthijs, Marie-Cecile Nassogne, Francois-Guillaume Debray, Dominique Roland, Teodora Chamova, Viktor Kozich, Jesina Pavel, Martin Zenker, Christina Lampe, Anihb Martin Das, Julia Hennermann, Stefan Koelker, Natalie Weinhold, Klaus Mohnike, Sarah Gruenert, Allan Meldgaard Lund, Montserrat Morales-Conejo, Mireia del Toro-Riera, Luis Aldamiz-Echevarria, Maria-Teresa Garcia-Silva, Manuel Schiff, Laurent Gouya, Philippe Labrune, Pascale de Lonlay, Nadia Belmatoug, Dominique P. Germain, Aline Cano, Dries Dobbelaere, Simon Jones, Charlotte Dawson, Patrick Deegan, Saikat Santra, Suresh Vijay, Danijela Petkovic Ramadza, Ivo Baric, Tamara Zigman, Gyoergy Pflieger, Katalin Szakszon, Rita Kaposta, Serena Gasperini, Alberto Burlina, Giancarlo Parenti, Pietro Strisciuglio, Giovanni Ceccarini, Antonio Federico, Alessandro Simonati, Birute Tumiene, Hidde Huidekoper, Francian van Spronsen, Annet Bosch, Maria-Estela Rubio-Gozalbo, Gepke Visser, Trine Tangeraas, Aasne Aarsand, Beata Kiec-Wilk, Ana-Maria Simoes Mendes Gaspar, Dulce Quelhas, Elisa Leao-Teles, Olga Azevedo, Esmeralda-Maria Ferreira Rodriges Silva, Luisa-Maria de Abreu Freire Diogo Matos, Esmeralda Martins, Svetlana Lajic, Niklas Darin, Urh Groselj, Mojca-Zerjav Tansek
ORPHANET JOURNAL OF RARE DISEASES
(2020)
Review
Endocrinology & Metabolism
Simon A. Jones, Deborah Marsden, Tony Koutsoukos, Jennifer Sniadecki, Karen Tylee, Sarah Phillippo, Emil Kakkis
MOLECULAR GENETICS AND METABOLISM
(2020)
Review
Endocrinology & Metabolism
Simon A. Jones, Margaret McGovern, Olivier Lidove, Roberto Giugliani, Pramod K. Mistry, Carlo Dionisi-Vici, Maria-Veronica Munoz-Rojas, Lubomyra Nalysnyk, Alison D. Schecter, Melissa Wasserstein
MOLECULAR GENETICS AND METABOLISM
(2020)
Article
Endocrinology & Metabolism
A. Broomfield, J. Sims, J. Mercer, P. Hensman, A. Ghosh, K. Tylee, K. M. Stepien, A. Oldham, N. Prathivadi Bhayankaram, R. Wynn, N. B. Wright, S. A. Jones, S. Wilkinson
Summary: The study focused on long-term pulmonary function outcomes of two cohorts of MPS I patients, HSCT-treated and ERT-treated, and found that all pediatrically diagnosed MPS I patients treated with therapies had restrictive lung disease, indicating its significance in morbidity. Further stratification including DLCO is needed to better understand the outcomes.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Genetics & Heredity
Rajkumar Sundarapandian, Simon Jones, Alexander Broomfield, Pauline Hensman, Neil Oxborrow
ORPHANET JOURNAL OF RARE DISEASES
(2020)
Review
Endocrinology & Metabolism
Berna Seker Yilmaz, James Davison, Simon A. Jones, Julien Baruteau
Summary: MPS III, a neurodegenerative disease, currently lacks disease-modifying therapy, but multiple curative therapies have been developed, emphasizing the importance of early treatment before extensive neuronal loss occurs.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Genetics & Heredity
Suresh Vijay, Anais Brassier, Arunabha Ghosh, Simona Fecarotta, Florian Abel, Sachin Marulkar, Simon A. Jones
Summary: The findings of the two studies on rapidly progressive LAL-D in infants demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival, improved growth and hematologic parameters, and was generally well tolerated.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Aimee Donald, Chong Y. Tan, Anupam Chakrapani, Derralyn A. Hughes, Reena Sharma, Duncan Cole, Stanislav Bardins, Martin Gorges, Simon A. Jones, Erich Schneider
ORPHANET JOURNAL OF RARE DISEASES
(2020)
Article
Genetics & Heredity
Bethanie Garside, Jan Hoong Ho, See Kwok, Yifen Liu, Shaishav Dhage, Rachelle Donn, Zohaib Iqbal, Simon A. Jones, Handrean Soran
Summary: Patients with NPD-B had a proatherogenic lipid profile and higher circulating TNF-alpha compared to the reference group. ERT treatment led to improvements in dyslipidaemia, including reductions in LDL-C and apoB100 levels, possibly driven by reductions in TNF-alpha and PCSK9.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Correction
Genetics & Heredity
Suresh Vijay, Anais Brassier, Arunabha Ghosh, Simona Fecarotta, Florian Abel, Sachin Marulkar, Simon A. Jones
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
George A. Diaz, Simon A. Jones, Maurizio Scarpa, Karl Eugen Mengel, Roberto Giugliani, Nathalie Guffon, Isabela Batsu, Patricia A. Fraser, Jing Li, Qi Zhang, Catherine Ortemann-Renon
Summary: The study evaluated olipudase alfa enzyme replacement therapy in children with ASMD, showing that the treatment was well-tolerated with significant improvements in disease pathology and various clinical endpoints.
GENETICS IN MEDICINE
(2021)
Article
Biophysics
R. Nataraj, P. Hiwarkar, D. Bonney, H. Campbell, S. Jones, D. Deambrosis, P. Evans, K. Poulton, P. M. van Hasselt, Mb Bierings, J. J. Boelens, C. A. Lindemans, R. Wynn
Summary: Umbilical cord blood is the preferred donor cell source for hematopoietic cell transplant in children with inherited metabolic disorders, as it is associated with improved engrafted survival and higher donor chimerism. Immune-mediated cytopenia and primary graft failure are common limitations in pediatric cord blood transplants for non-malignant diseases. Adding rituximab to the conditioning regimen has shown to improve event-free survival and reduce the incidence of graft failure in patients undergoing myeloablative conditioning for cord blood transplant.
BONE MARROW TRANSPLANTATION
(2022)
Letter
Biophysics
Su Han Lum, Milen Minkov, Simon A. Jones, Sheree Hazelaar, Tiarlan Sirait, Jane E. Potter, Polina Stepensky, Frederic Garban, Herbert Pichler, Jerry Stein, Zuhre Kaya, Ansgar Schulz, Karin Mellgren, Cristina Diaz de Heredia, Cecile Pochon, Susana Riesco, Miguel Angel Diaz, Gerard Michel, Caroline Lindemans, Bernd Gruhn, Michael H. Albert, Arjan C. Lankester, Benedicte Neven, Robert Wynn
BONE MARROW TRANSPLANTATION
(2023)
Article
Pediatrics
Claire Frauenfelder, Elizabeth Maughan, Johnny Kenth, Reema Nandi, Simon Jones, Robert Walker, Bill Walsh, Nagarajan Muthialu, Iain Bruce, Richard Hewitt, Colin Butler
Summary: The primary cause of death in Morquio A syndrome is airway obstruction. The debate regarding the underlying pathophysiology of the obstruction continues. Enzyme replacement therapy and multidisciplinary management have improved life expectancy, but alternatives to palliation of tracheal obstruction are needed.
CASE REPORTS IN PEDIATRICS
(2023)
Review
Biochemistry & Molecular Biology
Karolina M. Stepien, Neve Cufflin, Aimee Donald, Simon Jones, Heather Church, Iain P. Hargreaves
Summary: Mitochondrial dysfunction is a major factor in the pathophysiology of lysosomal storage disorders (LSDs). The cause of mitochondrial dysfunction in LSDs is not yet clear, but oxidative stress and impaired mitophagy are believed to be common inhibitory mechanisms. Many LSDs exhibit neurodegeneration and current therapies are inadequate. Therefore, novel therapeutic strategies targeting both mitochondrial and lysosomal impairment could be crucial for the long-term management of LSDs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)