Article
Multidisciplinary Sciences
Jannike Nickander, Ben Cole, Sabrina Nordin, Ravi Vijapurapu, Richard P. Steeds, James C. Moon, Peter Kellman, Martin Ugander, Rebecca Kozor
Summary: In a multicenter study of Fabry patients and healthy controls, blood-correction of myocardial native T1 was found to increase the number of patients with low T1 and reclassify them as having cardiac involvement. This blood-correction may potentially allow for earlier detection and therapy initiation.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Menno ter Huurne, Benjamin L. Parker, Ning Qing Liu, Elizabeth Ling Qian, Celine Vivien, Kathy Karavendzas, Richard J. Mills, Jennifer T. Saville, Dad Abu-Bonsrah, Andrea F. Wise, James E. Hudson, Andrew S. Talbot, Patrick F. Finn, Paolo G. V. Martini, Maria Fuller, Sharon D. Ricardo, Kevin I. Watt, Kathy M. Nicholls, Enzo R. Porrello, David A. Elliott
Summary: This study evaluated the efficacy of nucleoside-modified messenger RNA (modRNA) treatment for Fabry disease and validated it using a human cardiac model generated from induced pluripotent stem cells. The results showed that modRNA treatment restored α-Galactosidase A enzyme activity and reduced glycosphingolipid accumulation, demonstrating its therapeutic potential.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Pediatrics
Qian Li, Jing Wang, Minle Tian, Zhenle Yang, Lichun Yu, Suwen Liu, Cong Wang, Xiaoyuan Wang, Shuzhen Sun
Summary: This study retrospectively analyzed the clinical features, diagnosis, and enzyme replacement therapy (ERT) of 10 children with Fabry disease (FD). The results showed that the clinical manifestations of FD in children are diverse, and a definite diagnosis is necessary through the combination of family history, enzyme activity, biomarkers, gene testing, and other indicators. ERT with agalsidase alpha and beta can effectively reduce Lyso-GL-3 levels and achieve stable results.
FRONTIERS IN PEDIATRICS
(2023)
Review
Biochemistry & Molecular Biology
Olga Azevedo, Filipa Cordeiro, Miguel Fernandes Gago, Gabriel Miltenberger-Miltenyi, Catarina Ferreira, Nuno Sousa, Damiao Cunha
Summary: Fabry disease is an X-linked lysosomal storage disorder caused by GLA gene mutations, resulting in accumulation of GB3 in cardiac cells and leading to cardiac issues. Despite available therapies, cardiac involvement remains the main cause of death in patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jessica Gambardella, Antonella Fiordelisi, Federica Andrea Cerasuolo, Antonietta Buonaiuto, Roberta Avvisato, Alessandro Viti, Eduardo Sommella, Fabrizio Merciai, Emanuela Salviati, Pietro Campiglia, Valeria D'Argenio, Silvia Parisi, Antonio Bianco, Letizia Spinelli, Eugenio Di Vaia, Alberto Cuocolo, Antonio Pisani, Eleonora Riccio, Teodolinda Di Risi, Michele Ciccarelli, Gaetano Santulli, Daniela Sorriento, Guido Iaccarino
Summary: This study investigates the energetic mechanisms related to skeletal muscle pain and fatigue in Fabry disease. It finds that aerobic activity tolerance is reduced and lactate accumulation occurs in both mice and patients with Fabry disease. The upregulation of miR-17 and HIF-1 is linked to metabolic remodeling and the Warburg effect in Fabry disease. These findings suggest potential therapeutic targets and diagnostic/monitoring tools for Fabry disease.
Review
Chemistry, Medicinal
Muhammad Umer, Dinesh K. K. Kalra
Summary: Fabry disease is a rare genetic disorder that affects the metabolism of glycosphingolipids. It results in the accumulation of globotriaosylceramide in lysosomes due to a deficiency of the alpha-galactosidase A enzyme. This disease affects multiple organs, mainly the kidneys, heart, and cerebrovascular system. Early diagnosis and treatment are crucial in preventing irreversible tissue damage, organ failure, and life-threatening complications that can significantly impact life expectancy. This review focuses on the current and emerging treatment options for Fabry disease.
Article
Multidisciplinary Sciences
Gulfidan Bitirgen, Kultigin Turkmen, Nazmi Zengin, Rayaz A. Malik
Summary: This study found that abnormal pupillary responses to white light stimulation in patients with Fabry disease are associated with the severity of autonomic symptoms.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Malte Lenders, Solvey Pollmann, Melina Terlinden, Eva Brand
Summary: In this study, the cross-reactivity of anti-drug antibodies (ADAs) against agalsidase-alfa and-beta and the novel PEGylated enzyme pegunigalsidase-alfa (PRX-102) was analyzed in Fabry disease patients. The results showed that PRX-102 had masked epitopes and lower affinity for ADAs compared to agalsidase-alfa and-beta, but strong inhibitory capacities were still observed. Therefore, switching to PRX-102 therapy may benefit ADA-affected patients.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Review
Neurosciences
Lina Palaiodimou, Panagiotis Kokotis, Christina Zompola, Georgia Papagiannopoulou, Eleni Bakola, Marianna Papadopoulou, Vasiliki Zouvelou, Dimitrios Petras, Charalampos Vlachopoulos, Georgios Tsivgoulis
Summary: This narrative review discusses the current and novel therapeutic strategies in Fabry disease (FD), including symptomatic and specific treatments. A multidisciplinary symptomatic treatment is recommended, personalized according to disease manifestations. FD-specific treatments such as enzyme-replacement-therapies and chaperone treatment have been approved, and other treatment options are currently under investigation.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Urology & Nephrology
Il Young Kim, Hyun Jung Lee, Chong Kun Cheon
Summary: This study found that segmental foot process effacement and GL3 deposits may persist in Fabry nephropathy despite enzyme replacement therapy. Additionally, segmental foot process effacement and GL3 deposits were observed in various kidney cells in normoalbuminuric patients with Fabry disease.
KIDNEY RESEARCH AND CLINICAL PRACTICE
(2021)
Article
Multidisciplinary Sciences
William C. Hallows, Kristen Skvorak, Nick Agard, Nikki Kruse, Xiyun Zhang, Yu Zhu, Rachel C. Botham, Chinping Chng, Charu Shukla, Jessica Lao, Mathew Miller, Antoinette Sero, Judy Viduya, Moulay Hicham Alaoui Ismaili, Kerryn McCluskie, Raphael Schiffmann, Adam P. Silverman, Jin-Song Shen, Gjalt W. Huisman
Summary: Fabry disease is caused by a deficiency of α-galactosidase A (GLA), resulting in the accumulation of glycosphingolipids. Directed evolution was used to generate more stable GLA variants, such as GLAv05 and GLAv09, which showed improved stability, enzyme activity, and pharmacokinetics. These findings hold promise for more effective treatments of lysosomal storage diseases.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Fabian Braun, Ahmed Abed, Dominik Sellung, Manuel Rogg, Mathias Woidy, Oysten Eikrem, Nicola Wanner, Jessica Gambardella, Sandra D. Laufer, Fabian Haas, Milagros N. Wong, Bernhard Dumoulin, Paula Rischke, Anne Muehlig, Wiebke Sachs, Katharina von Cossel, Kristina Schulz, Nicole Muschol, Soeren W. Gersting, Ania C. Muntau, Oliver Kretz, Oliver Hahn, Markus M. Rinschen, Michael Mauer, Tillmann Bork, Florian Grahammer, Wei Liang, Thorsten Eierhoff, Winfried Roemer, Arne Hansen, Catherine Meyer-Schwesinger, Guido Iaccarino, Camilla Tondel, Hans-Peter Marti, Behzad Najafian, Victor G. Puelles, Christoph Schell, Tobias B. Huber
Summary: Current therapies for Fabry disease, such as enzyme replacement therapy (ERT), aim to reduce globotriaosylceramide (Gb3) accumulation, but their effect on reversing end-organ damage remains unclear. This study showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Modulating α-synuclein (SNCA) showed more beneficial effects in improving lysosomal structure and function in Fabry podocytes compared to ERT. This research highlights the importance of considering SNCA modulation as a potential intervention for Fabry nephropathy.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Pediatrics
Jenny Avarappattu, Ariana Gaspert, Giuseppina Sparta, Marianne Rohrbach
Summary: This study examined kidney biopsies of untreated children with Fabry disease to determine if early initiation of enzyme replacement therapy (ERT) is warranted. The findings showed that histological lesions characteristic of Fabry disease can be observed in young patients without typical clinical symptoms or laboratory abnormalities, suggesting that kidney biopsies may be a useful tool for early diagnosis of renal involvement in Fabry disease. Early initiation of ERT should be considered based on these biopsy findings without clinical correlation.
PEDIATRIC NEPHROLOGY
(2023)
Article
Psychiatry
Merel M. Nap-van der Vlist, Anouk Vroegindeweij, Johanna W. Hoefnagels, Cornelis K. van der Ent, Joost F. Swart, Elise M. van de Putte, Sanne L. Nijhof
Summary: The objective of this study was to examine the validity of the paediatric Short Fatigue Questionnaire (pSFQ) for assessing subjective fatigue in children, and to provide a cut-off score for severe fatigue. The results showed that the pSFQ is a practical and reliable screening tool for evaluating severe fatigue in children with or without a chronic disease.
JOURNAL OF PSYCHOSOMATIC RESEARCH
(2023)
Article
Medicine, General & Internal
Markus Cybulla, Kathleen Nicholls, Sandro Feriozzi, Ales Linhart, Joan Torras, Bojan Vujkovac, Jaco Botha, Christina Anagnostopoulou, Michael L. West
Summary: This study evaluated the impact of agalsidase alfa on renal decline in patients with Fabry disease, finding that patients with high baseline proteinuria had a faster decline in eGFR, while the decline in eGFR in classic Fabry disease patients was not associated with baseline proteinuria. This suggests that early treatment and good proteinuria control may play a significant role in renal protection.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Nanoscience & Nanotechnology
Ibane Abasolo, Joaquin Seras-Franzoso, Marc Molto-Abad, Vanessa Diaz-Riascos, Jose Luis Corchero, Guillem Pintos-Morell, Simo Schwartz Jr
Summary: Lysosomal storage disorders are rare diseases where enzyme replacement therapy is the main treatment method, but it has limitations. Nanotechnology-based drug delivery systems have been proposed as a solution to overcome these limitations and improve the effectiveness of enzyme replacement therapy.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2021)
Article
Genetics & Heredity
Patricia Haug, Samuel Koller, Jordi Maggi, Elena Lang, Silke Feil, Agnes Wlodarczyk, Luzy Bahr, Katharina Steindl, Marianne Rohrbach, Christina Gerth-Kahlert, Wolfgang Berger
Summary: Coloboma and microphthalmia (C/M) are related congenital eye malformations that exhibit significant genetic heterogeneity, as revealed by a study utilizing high throughput DNA sequencing technologies. The study identified novel gene variants and potentially disease-causing genes in a portion of C/M patients, including three de novo mutations. This highlights the diagnostic power of whole-exome sequencing for genetic screening in patients and families with C/M.
Review
Medicine, General & Internal
Uma Ramaswami, Simona D'Amore, Niamh Finnegan, Derralynn Hughes, Masoud Kazemi
Summary: This study evaluates the impact of the COVID-19 pandemic on the lysosomal disorders unit at Royal Free London NHS Foundation Trust, highlighting changes in home care and emergency care, development of new clinical pathways, staff redeployment, and patient adaptations. Lessons learned from this highly specialised service during the pandemic may be applicable to other rare disease services for future readiness.
INTERNAL MEDICINE JOURNAL
(2021)
Article
Genetics & Heredity
Pei Jin Lim, Severin Marfurt, Uschi Lindert, Lennart Opitz, Timothee Ndarugendamwo, Pakeerathan Srikanthan, Martin Poms, Martin Hersberger, Claus-Dieter Langhans, Dorothea Haas, Marianne Rohrbach, Cecilia Giunta
Summary: Osteogenesis imperfecta is an inherited disorder characterized by low bone density, bone fragility, and recurrent fractures. Mutations in the MBTPS2 gene may affect fatty acid metabolism or cartilage development, potentially impacting bone development and mineralization.
FRONTIERS IN GENETICS
(2021)
Article
Pediatrics
Christina T. Ruesch, Ursula Knirsch, Daniel M. Weber, Marianne Rohrbach, Andre Eichenberger, Juerg Luetschg, Kirsten Weber, Philip J. Broser, Georg M. Stettner
Summary: Carpal tunnel syndrome in childhood is rare and primarily caused by underlying disorders, with mucopolysaccharidosis being the most common underlying condition. Thorough evaluation and search for causative conditions are recommended for pediatric patients with CTS.
Article
Genetics & Heredity
Lucia Micale, Silvia Morlino, Annalucia Carbone, Annamaria Carissimo, Grazia Nardella, Carmela Fusco, Orazio Palumbo, Annalisa Schirizzi, Federica Russo, Gianluigi Mazzoccoli, Jeroen Breckpot, Chiara De Luca, Alessandro Ferraris, Cecilia Giunta, Paola Grammatico, Maria K. Haanpaa, Giorgia Mancano, Giulia Forzano, Davide Cacchiarelli, Hilde Van Esch, Bert Callewaert, Marianne Rohrbach, Marco Castori
Summary: This study describes a multisystem disorder caused by heterozygous loss-of-function variants in the TAB2 gene, involving cardiovascular, facial, musculoskeletal, and cutaneous anomalies.
GENETICS IN MEDICINE
(2022)
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)
Article
Medicine, General & Internal
Simona D'Amore, Navdeep Kumar, Uma Ramaswami
Summary: Gaucher disease is a metabolic disorder caused by a deficiency of the enzyme glucocerebrosidase, resulting in the accumulation of glucocerebroside in macrophage lysosomes. Clinical presentation varies widely and commonly includes hepatosplenomegaly, pancytopenia, and bone abnormalities. This case describes jaw involvement in a 63-year-old patient with type 1 Gaucher disease, who had a history of long-term bisphosphonate use.
Article
Medicine, General & Internal
Josephine Norre Hogh, Hatim Ebrahim, Shabbir Moochhala, Uma Ramaswami
Summary: This case report presents a case of an 11-year-old boy with Fabry disease presenting with early-stage renal failure requiring dialysis and transplant. The diagnosis was confirmed by renal biopsy, gene mutation, and enzyme level tests. Early and accelerated disease progression should be considered in males with unexplained renal failure at a young age.
Review
Genetics & Heredity
Michael Beck, Uma Ramaswami, Elizabeth Hernberg-Stahl, Derralynn A. Hughes, Christoph Kampmann, Atul B. Mehta, Kathleen Nicholls, Dau-Ming Niu, Guillem Pintos-Morell, Ricardo Reisin, Michael L. West, Jorn Schenk, Christina Anagnostopoulou, Jaco Botha, Roberto Giugliani
Summary: The Fabry Outcome Survey (FOS) is a long-term observational registry aimed at broadening the understanding of Fabry disease and improving the clinical management of affected patients. Over the past 20 years, FOS has enrolled 4484 diagnosed patients from 144 centers across 26 countries and has published nearly 60 manuscripts on various topics related to Fabry disease. Analyses of FOS data have provided valuable insights into the natural history of the disease, the effectiveness of treatment, and specific populations affected by Fabry disease. FOS has greatly contributed to the scientific knowledge and patient management of this rare disease.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Hematology
Clara Carnicer-Caceres, Yolanda Villena-Ortiz, Laura Castillo-Ribelles, Raquel Barquin-del-Pino, Maria Camprodon-Gomez, Ana Felipe-Rucian, David Moreno-Martinez, Sara Lucas-del-Pozo, Jorge Hernandez-Vara, Anna Garcia-Serra, Ariadna Tigri-Santina, Marc Molto-Abad, Irene Agraz-Pamplona, Jose F. Rodriguez-Palomares, Javier Limeres-Freire, Marc Macaya-Font, Victor Rodriguez-Sureda, Lucy Dougherty-De Miguel, Mireia del-Toro-Riera, Guillem Pintos-Morell, Jose Antonio Arranz-Amo
Summary: Lysosomal storage disorders are inherited metabolic diseases caused by a deficiency of lysosomal hydrolases, and the clinical orientation greatly influences the diagnostic yield of enzymatic tests, which can guide subsequent genetic testing.
BLOOD CELLS MOLECULES AND DISEASES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Simona D'Amore, Hiroshige Sano, Daniel David George Chappell, Davide Chiarugi, Olivia Baker, Kathleen Page, Uma Ramaswami, Fjola Johannesdottir, Timothy M. Cox, Patrick Deegan, Kenneth E. Poole
Summary: Radiographic cortical thickness index of 0.50 or less was found to be a reliable predictor of fracture risk in patients with Gaucher disease.
Article
Pediatrics
Jenny Avarappattu, Ariana Gaspert, Giuseppina Sparta, Marianne Rohrbach
Summary: This study examined kidney biopsies of untreated children with Fabry disease to determine if early initiation of enzyme replacement therapy (ERT) is warranted. The findings showed that histological lesions characteristic of Fabry disease can be observed in young patients without typical clinical symptoms or laboratory abnormalities, suggesting that kidney biopsies may be a useful tool for early diagnosis of renal involvement in Fabry disease. Early initiation of ERT should be considered based on these biopsy findings without clinical correlation.
PEDIATRIC NEPHROLOGY
(2023)
Review
Peripheral Vascular Disease
Steve E. Humphries, Uma Ramaswami, Neil Hopper
Summary: FH meets all the criteria and principles for inclusion in the Newborn Genomes Programme, and should therefore be included.
CURRENT ATHEROSCLEROSIS REPORTS
(2023)
Article
Medicine, General & Internal
Federico Baronio, Stefano Zucchini, Francesco Zulian, Mariacarolina Salerno, Rossella Parini, Alessandro Cattoni, Federica Deodato, Alberto Gaeta, Carla Bizzarri, Serena Gasperini, Andrea Pession
Summary: Diagnostic delay is common in MPS Ia due to the rarity of the disease and the variability of clinical presentation. A multidisciplinary panel developed an algorithm to improve awareness and reduce diagnostic delay of MPS Ia in pediatric endocrinologists.
MEDICINA-LITHUANIA
(2022)