Review
Biochemistry & Molecular Biology
Christiane S. Hampe, Brianna D. Yund, Paul J. Orchard, Troy C. Lund, Jacob Wesley, R. Scott McIvor
Summary: MPS I and II are two closely related lysosomal storage diseases with disruptions in glycosaminoglycan catabolism. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while MPS II is dominated by HS levels and higher sulfation levels. The differences in phenotypical manifestations and neurological involvement between MPS I and II are likely due to these differences in glycosaminoglycan ratios and sulfation levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
E. Yu Voskoboeva, T. M. Bookina, A. N. Semyachkina, S. V. Mikhaylova, N. D. Vashakmadze, G. V. Baydakova, E. Yu Zakharova, S. I. Kutsev
Summary: This article presents the results of a molecular genetic study on 206 patients with mucopolysaccharidosis type I (MPS I) from the Russian Federation and other republics of the former Soviet Union. The study found differences in the distribution of IDUA gene mutations among different populations and ethnic groups. The identified features are important for understanding the molecular origin of the disease, predicting the risk of its development, and creating optimal diagnostic and treatment tools for specific regions and ethnic groups.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Genetics & Heredity
Federico Spataro, Fabio Viggiani, Domenico Giorgio Macchia, Valentina Rollo, Albina Tummolo, Patrizia Suppressa, Carlo Sabba', Maria Pia Rossi, Lucia Giliberti, Francesco Satriano, Eustachio Nettis, Danilo Di Bona, Maria Filomena Caiaffa, Rita Fischetto, Luigi Macchia
Summary: This study investigated the rapid desensitization treatment for Idursulfase and laronidase allergy, combined with subcutaneous allergen immunotherapy-like desensitization. This approach restored long-term tolerance and allowed patients to receive enzyme replacement therapy according to the normal administration schedule.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Endocrinology & Metabolism
Victor Kovac, Elsa G. Shapiro, Kyle D. Rudser, Bryon A. Mueller, Julie B. Eisengart, Kathleen A. Delaney, Alia Ahmed, Kelly E. King, Brianna D. Yund, Morton J. Cowan, Julian Raiman, Eva G. Mamak, Paul R. Harmatz, Suma P. Shankar, Nadia Ali, Stephanie R. Cagle, Jeffrey R. Wozniak, Kelvin O. Lim, Paul J. Orchard, Chester B. Whitley, Igor Nestrasil
Summary: In this study, we used a quantitative MRI protocol to compare the brain macrostructure between individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC). We found significant differences in cortical and subcortical gray matter, white matter, corpus callosum, ventricular, and choroid plexus volumes between MPS I participants and HC. The severity of MPS I, age, and cognition had effects on these brain structures. We also observed age-related differences in neurodevelopmental trajectories between MPS I forms and HC.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Biophysics
Antoine Gardin, Martin Castelle, Samia Pichard, Aline Cano, Brigitte Chabrol, Julie Piarroux, Agathe Roubertie, Yann Nadjar, Anne-Sophie Guemann, Marine Tardieu, Didier Lacombe, Matthieu P. Robert, Catherine Caillaud, Roseline Froissart, Virginie Leboeuf, Valerie Barbier, Juliette Bouchereau, Manuel Schiff, Brigitte Fauroux, Briac Thierry, Romain Luscan, Syril James, Timothee de Saint-Denis, Stephanie Pannier, Cyril Gitiaux, Estelle Vergnaud, Nathalie Boddaert, Claire Lascourreges, Michel Lemoine, Damien Bonnet, Stephane Blanche, Jean-Hugues Dalle, Benedicte Neven, Pascale de Lonlay, Anais Brassier
Summary: MPS I-H is a rare lysosomal storage disorder caused by alpha-L-Iduronidase deficiency. Early hematopoietic stem cell transplantation (HSCT) is the only available therapeutic option to preserve neurocognitive functions. A long-term follow-up of MPS I-H patients who underwent HSCT showed good outcomes in terms of chimerism, enzyme activity, language acquisition, and socio-professional insertion. However, skeletal dysplasia and sensory impairments progressed despite HSCT, indicating the need for further treatment options such as gene therapy.
BONE MARROW TRANSPLANTATION
(2023)
Review
Biochemistry & Molecular Biology
Christiane S. Hampe, Jacob Wesley, Troy C. Lund, Paul J. Orchard, Lynda E. Polgreen, Julie B. Eisengart, Linda K. McLoon, Sebahattin Cureoglu, Patricia Schachern, R. Scott McIvor
Summary: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA), with severe and attenuated forms. Approved treatments include enzyme replacement therapy and hematopoietic stem cell transplantation, which improve disease manifestations but do not completely alleviate symptoms. Early diagnosis and treatment are crucial for preventing disease progression.
Article
Medicine, Research & Experimental
Elizabeth Hwang-Wong, Gabrielle Amar, Nanditha Das, Xiaoli Zhang, Nina Aaron, Kirsten Gale, Nyanza Rothman, Massimo Fante, Andrew Baik, Ajay Bhargava, Arun Fricker, Michelle Mcalister, Jeremy Rabinowitz, John Lees-Shepard, Kalyan Nannuru, Aris N. Economides, Katherine D. Cygnar
Summary: This study reveals the importance of early intervention in improving skeletal phenotypes in Mucopolysaccharidosis VI (MPS VI). Current enzyme replacement therapy shows limited efficacy in treating the skeletal manifestations of MPS VI.
Article
Pediatrics
Ying Li, Deyun Liu, Yue Yu
Summary: Mucopolysaccharidosis is a rare disease with seven different subtypes based on the affected enzyme. This study reports on the successful treatment of a Chinese boy with mucopolysaccharidosis type I using enzyme replacement therapy.
FRONTIERS IN PEDIATRICS
(2022)
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
Endocrinology & Metabolism
Nishitha R. Pillai, Sara A. Elsbecker, Ashish O. Gupta, Troy C. Lund, Paul J. Orchard, Elizabeth Braunlin
Summary: In this study, the addition of continuous milrinone infusion during hematopoietic cell transplantation (HCT) was found to be effective in improving cardiac function in infants with severe mucopolysaccharidosis type I (MPS IH) whose cardiac systolic function failed to normalize with enzyme replacement therapy (ERT) alone. All patients experienced a recovery in cardiac function after HCT, with only one patient experiencing sepsis-related death during the procedure.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Cardiac & Cardiovascular Systems
Elizabeth Braunlin, Luisa Bay, Nathalie Guffon, Meng Yang, Nicolas Pangaud, Lorne A. Clarke
Summary: Mucopolysaccharidosis type I is a genetic disease with common cardiovascular involvement, and there are differences in the types and progression of cardiac abnormalities between the severe and attenuated phenotypes.
CARDIOLOGY IN THE YOUNG
(2023)
Article
Genetics & Heredity
Antonio Toscano, Olimpia Musumeci, Michele Sacchini, Sabrina Ravaglia, Gabriele Siciliano, Agata Fiumara, Elena Verrecchia, Melania Maione, Jennifer Gentile, Rita Fischetto, Grazia Crescimanno, Roberta Taurisano, Annalisa Sechi, Serena Gasperini, Vittoria Cianci, Lorenzo Maggi, Rossella Parini, Antonino Lupica, Maurizio Scarpa
Summary: This study analyzed the safety, treatment satisfaction, and compliance of MPS I and Pompe disease patients treated with laronidase and alglucosidase alfa in a homecare setting. The results showed that home therapy had a favorable safety profile and improved treatment compliance and personal satisfaction.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Biotechnology & Applied Microbiology
Torayuki Okuyama, Yoshikatsu Eto, Norio Sakai, Kimitoshi Nakamura, Tatsuyoshi Yamamoto, Mariko Yamaoka, Toshiaki Ikeda, Sairei So, Kazunori Tanizawa, Hiroyuki Sonoda, Yuji Sato
Summary: The study demonstrated that pabinafusp alfa is a potentially effective treatment for both the central and peripheral symptoms of MPS-II patients, with the ability to cross the blood-brain barrier to reach the central nervous system. In the 52-week clinical trial, the drug showed relatively good efficacy and safety profiles.
Article
Genetics & Heredity
Dan Wang, Xiaojiao Xue, Gwen Gunn, Ming Du, Amna Siddiqui, Marla Weetall, Kim M. Keeling
Summary: This article investigates the effectiveness of Ataluren as a readthrough agent and its mechanism in suppressing premature termination codons (PTCs). The research found that Ataluren promotes readthrough of PTCs in various models and also reduces symptoms caused by a specific nonsense mutation associated with a genetic disease. Additionally, the article points out that Ataluren has a bell-shaped dose-response curve and a narrow effective range.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Biochemistry & Molecular Biology
Magdalena Machnikowska-Sokolowska, Aleksandra Myszczuk, Emilia Wieszala, Dominika Wieja-Blach, Ewa Jamroz, Justyna Paprocka
Summary: Mucopolysaccharidosis 1 (MPS 1) is a rare lysosomal genetic disorder that causes the accumulation of undegraded glycosaminoglycans (GAGs) in the body, resulting in multiorgan damage. Neurological symptoms can range from mild to severe. Neuroimaging, especially magnetic resonance imaging (MRI), plays a crucial role in diagnosing and monitoring this disease. Early diagnosis is essential for timely therapy implementation. New imaging tools such as MR spectroscopy (MRS), semiquantitative MRI analysis, and scoring systems greatly assist in surveillance of MPS 1. This analysis is based on 5 children with MPS 1 and a review of the literature, highlighting the importance of radiologists' vigilance and knowledge of neuroradiological patterns.
Article
Genetics & Heredity
Simone Silva dos Santos-Lopes, Jessica Maria Florencio de Oliveira, Denise de Queiroga Nascimento, Yorran Hardman Araujo Montenegro, Sandra Leistner-Segal, Ana Carolina Brusius-Facchin, Catia Eufrazino Gondim, Roberto Giugliani, Paula Frassinetti Vasconcelos de Medeiros
Summary: The study found that most MPS IVA patients have European paternal ancestry and observed high levels of consanguinity as well as intra-familial phenotypic heterogeneity.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Roberto Giugliani, Anneliese Lopes Barth, Melissa Rossi Calvao Dumas, Jose Francisco da Silva Franco, Liane de Rosso Giuliani, Carlos Henrique Paiva Grangeiro, Dafne Dain Gandelman Horovitz, Chong Ae Kim, Emilia Katiane Embirucu de Araujo Leao, Paula Frassinetti Vasconcelos de Medeiros, Diego Santana Chaves Geraldo Miguel, Maria Espirito Santo Almeida Moreira, Helena Maria Guimaraes Pimentel dos Santos, Luiz Carlos Santana da Silva, Luiz Roberto da Silva, Isabel Neves de Souza, Tatiele Nalin, Daniel Garcia
Summary: MPS VII, also known as Sly syndrome, is a rare disorder caused by deficiency of the lysosomal enzyme beta-glucuronidase. A case series report on MPS VII patients in Brazil found common clinical features such as coarse face, non-immune hydrops fetalis, short neck and trunk, neurodevelopmental delay, and cognitive impairment. This study provides important clinical data for MPS VII patients in Latin America.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Fernanda Medeiros Sebastiao, Kristiane Michelin-Tirelli, Fernanda Bender, Franciele Fatima Lopes, Inamara Moraes, Francyne Kubaski, Roberto Giugliani, Maira Burin
Summary: The COVID-19 pandemic significantly reduced the number of tests and diagnoses for patients with Inborn Errors of Metabolism (IEM) in Brazil, leading to a significant underdiagnosis of IEM.
GENETICS AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Roberto Giugliani, Ana Maria Martins, Torayuki Okuyama, Yoshikatsu Eto, Norio Sakai, Kimitoshi Nakamura, Hideto Morimoto, Kohtaro Minami, Tatsuyoshi Yamamoto, Mariko Yamaoka, Toshiaki Ikeda, Sairei So, Kazunori Tanizawa, Hiroyuki Sonoda, Mathias Schmidt, Yuji Sato
Summary: This article discusses the effectiveness of enzyme replacement therapy on MPS patients and the significant progress in addressing central nervous system symptoms in MPS-II patients with pabinafusp alfa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Amanda Bingaman, Christine Waggoner, Sara M. Andrews, Diana Pangonis, Marie Trad, Roberto Giugliani, Ruben Giorgino, Jeanine Jarnes, Rojan Vakili, Victoria Ballard, Holly L. Peay
Summary: GM1-gangliosidosis (GM1) is a rare neurodegenerative disorder that leads to early mortality and progressive decline of physical skills and cerebral functioning. This study is the first to explore the priorities of parents of children with pediatric onset forms of GM1. The study identifies the symptoms most critical to caregivers and provides important insights for the development of patient-focused treatments.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Health Care Sciences & Services
Fabiano de Oliveira Poswar, Johanna Henriques Nehm, Francyne Kubaski, Edina Poletto, Roberto Giugliani
Summary: This review summarizes the clinical manifestations, diagnosis, and emerging treatments for Mucopolysaccharidosis VII (MPS VII), a rare lysosomal disease caused by a deficiency of the enzyme beta-glucuronidase (GUS).
THERAPEUTICS AND CLINICAL RISK MANAGEMENT
(2022)
Review
Genetics & Heredity
Michael H. Gelb, Khaja Basheeruddin, Alberto Burlina, Hsiao-Jan Chen, Yin-Hsiu Chien, George Dizikes, Christine Dorley, Roberto Giugliani, Amy Hietala, Xinying Hong, Shu-Min Kao, Hamid Khaledi, Tracy Klug, Francyne Kubaski, Hsuan-Chieh Liao, Monica Martin, Adrienne Manning, Joseph Orsini, Yin Peng, Enzo Ranieri, Andreas Rohrwasser, Nicolas Szabo-Fresnais, Coleman T. Turgeon, Frederick M. Vaz, Li-yun Wang, Dietrich Matern
Summary: Tandem mass spectrometry is the most commonly used platform for analyzing enzymatic activities and biomarkers in newborn screening. Liquid chromatography combined with mass spectrometry has been employed to reduce false-positive rates and screen for new conditions. The maintenance requirements for LC-MS/MS and FIA-MS/MS systems are similar, but LC-MS/MS offers higher screening efficiency and turnaround time.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2022)
Review
Biotechnology & Applied Microbiology
Edina Poletto, Andrew Oliveira Silva, Ricardo Weinlich, Priscila Keiko Matsumoto Martin, Davi Coe Torres, Roberto Giugliani, Guilherme Baldo
Summary: Lysosomal storage disorders (LSD) are rare genetic diseases caused by mutations in lysosomal function-related genes. Gene therapy is a promising approach for LSD due to their monogenic nature and the ability of lysosomal proteins to cross-correct neighboring cells. Ex vivo gene therapy using modified cells from various sources, such as stem cells and hematopoietic precursors, is underway.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Article
Pharmacology & Pharmacy
Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler
Summary: Mucopolysaccharidosis (MPS) is a rare group of metabolic diseases with limited treatment options. This study proposes the use of immunomodulatory drugs in innovative individual treatment trials (ITTs) for MPS patients and develops a risk-benefit model for drug evaluation. The decision analysis framework (DAF) includes literature analysis, quantitative risk-benefit assessment, and phenotypic profiling. Four immunomodulatory drugs, adalimumab, abatacept, anakinra, and cladribine, show promise for MPS treatment. This evidence-based model provides a step towards precision medicine in MPS using immunomodulators.
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.
Retraction
Pharmacology & Pharmacy
Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler
Article
Genetics & Heredity
Francyne Kubaski, Alberto Burlina, Giulia Polo, Danilo Pereira, Zackary M. Herbst, Camilo Silva, Franciele B. Trapp, Kristiane Michelin-Tirelli, Franciele F. Lopes, Maira G. Burin, Ana Carolina Brusius-Facchin, Alice B. O. Netto, Larissa Faqueti, Gabrielle D. Iop, Edina Poletto, Roberto Giugliani
Summary: This study investigated the use of a two-tier approach for the detection of Niemann-Pick disease type C (NPC). The results showed elevated levels of lysosphingomyelin 509 (LysoSM509) in dried blood spots (DBS) of suspected NPC patients. Variants related to the disease were identified in the NPC1 and NPC2 genes. The quantification of LysoSM509 in DBS as a first-tier test improved the detection rate of NPC.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2022)
Article
Veterinary Sciences
Andreza Da Silva Amaral, Nathali Adrielli Agassi De Sales, Isabel Rodrigues Rosado, Roberto Giugliani, Maira Graeff Burin, Guilherme Baldo, Ian Martin, Endrigo Gabellini Leonel Alves
Summary: MPS are a group of rare diseases caused by deficient enzyme activity, leading to GAG accumulation in lysosomes and affecting patients' quality of life and lifespan. MPS type I in dogs presents with multisystem clinical signs, mainly including bone defects and visceral organ enlargement. Diagnostic methods consist of urine GAG quantification and blood enzymatic analysis.
ACTA SCIENTIAE VETERINARIAE
(2021)
Article
Pediatrics
Roberto Giugliani, Nicole Muschol, Hillary A. Keenan, Mark Dant, Joseph Muenzer
Summary: The study found that the times to diagnosis and HSCT initiation for individuals with severe MPS I remained consistent over the past 15 years, while the time to ERT initiation for individuals with attenuated MPS I has significantly improved, but the median age at diagnosis has not improved. Efforts are needed to improve early diagnosis in attenuated MPS I.
ARCHIVES OF DISEASE IN CHILDHOOD
(2021)
Article
Endocrinology & Metabolism
Esteban Alberto Gonzalez, Santiago Alonso Tobar Leitao, Douglas dos Santos Soares, Angela Maria Vicente Tavares, Roberto Giugliani, Guilherme Baldo, Ursula Matte
Summary: MPS I, caused by mutations in the IDUA gene, leads to heart complications in patients. Studies suggest that losartan and propranolol can improve cardiac function in MPS I mice, potentially serving as adjunctive treatment options.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)