Review
Medicine, General & Internal
Camille Bouchard, Jacques P. Tremblay
Summary: This review article presents 39 genes associated with limb-girdle muscular dystrophies (LGMDs), which can be inherited dominantly or recessively. The classification of LGMDs has evolved over time and now requires a mutation causing proximal muscle weakness found in multiple unrelated families. The article also discusses available and developing therapies for LGMDs, aiming to address the root cause of the disease instead of treating individual symptoms.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Genetics & Heredity
Sivan Lewis, Amy Woroch, Mary Kate Hatch, Reymundo Lozano
Summary: Limb-girdle muscular dystrophies are genetic disorders characterized by progressive proximal muscle weakness. This case report highlights the association between a specific variant in the SGCA gene and neurodevelopmental disorders in a 3-year-old boy with muscular weakness and elevated CK levels.
Article
Clinical Neurology
Eric M. Libell, Noelle C. Bowdler, Carrie M. Stephan, Miriam Bridget Zimmerman, Amber M. Gedlinske, Katherine D. Mathews
Summary: This study investigated the experiences and outcomes of pregnancy in women with LGMDR9, finding that most pregnancies were uncomplicated but may require assisted vaginal delivery and could lead to progression of weakness. More research on pregnancy in specific LGMD subtypes is needed to confirm these findings and determine if risks vary by genotype.
Article
Clinical Neurology
Martin Krenn, Matthias Tomschik, Matias Wagner, Gudrun Zulehner, Rosa Weng, Jakob Rath, Sigrid Klotz, Ellen Gelpi, Gabriel Bsteh, Omar Keritam, Isabella Colonna, Chiara Paternostro, Fiona Jaeger, Elisabeth Lindeck-Pozza, Stephan Iglseder, Susanne Grinzinger, Martina Schoenfelder, Christina Hohenwarter, Manfred Freimueller, Norbert Embacher, Julia Wanschitz, Raffi Topakian, Ana Toepf, Volker Straub, Stefan Quasthoff, Fritz Zimprich, Wolfgang N. Loescher, Hakan Cetin
Summary: The study focused on hereditary myopathies with limb-girdle muscular weakness (LGW) and found that using next-generation sequencing (NGS) earlier in the diagnostic process is necessary to avoid long delays in diagnosis. Parameters predictive of a molecular diagnosis were identified, which can help select patients for genetic analyses, especially in centers with limited access to sequencing technology.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anabel Rico, Garazi Guembelzu, Valle Palomo, Ana Martinez, Ana Aiastui, Leire Casas-Fraile, Andrea Valls, Adolfo Lopez de Munain, Amets Saenz
Summary: LGMDR1 is an autosomal recessive muscular dystrophy caused by mutations in the CAPN3 gene, with no cure currently available. Studies have shown a significant reduction in key protein expression and phosphorylation in the Wnt and mTOR signaling pathways in the muscles of LGMDR1 patients. Treatment options such as tideglusib and VP0.7 may restore the expression and phosphorylation of these proteins in LGMDR1 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Jose Luis Garcia-Gimenez, Elena R. Garcia-Trevijano, Ana Aviles-Alia, Jose Santiago Ibanez-Cabellos, Miquel Bovea-Marco, Teresa Bas, Federico Pallardo, Juan R. Vina, Rosa Zaragoza
Summary: This study identified a potential molecular signature consisting of circulating miR-122-5p/miR-192-5p/miR-323-3p and biochemical parameters that could be used for prognosis and stratification of patients with limb-girdle muscular dystrophy (LGMD).
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Chemistry, Medicinal
Lizzia Raffaghello, Elisa Principi, Serena Baratto, Chiara Panicucci, Sara Pintus, Francesca Antonini, Genny Del Zotto, Andrea Benzi, Santina Bruzzone, Paolo Scudieri, Carlo Minetti, Elisabetta Gazzerro, Claudio Bruno
Summary: In this study, the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079, was evaluated in limb-girdle muscular dystrophy R3. The results showed that the P2X7 antagonist improved clinical parameters, reduced muscle inflammation and fibrosis, and upregulated immunosuppressive regulatory T cells.
Article
Biochemistry & Molecular Biology
Patrizia Spadafora, Antonio Qualtieri, Francesca Cavalcanti, Gemma Di Palma, Olivier Gallo, Selene De Benedittis, Annamaria Cerantonio, Luigi Citrigno
Summary: This study reports a new missense variant in the DYSF gene associated with LGMDR2/2B, identified through NGS technology. The variant was found in homozygosity in two sisters of the proband, indicating its probable pathological role in the onset of the disease. The study highlights the potential of NGS as a powerful tool for identifying LGMD subtypes and emphasizes the importance of collecting and sharing genetic data for further genetic-molecular research and personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Lais U. Aivazoglou, Julio B. Guimaraes, Maria Alice F. Costa, Andre Yui Aihara, Fabiano N. Cardoso, Wladimir B. V. De R. Pinto, Paulo Victor S. de Souza, Andre M. S. da Silva, Edmar Zanoteli, Acary S. B. Oliveira, Alzira A. S. Carvalho, Artur Da R. C. Fernandes
Summary: This study aimed to correlate MRI findings with functional scores and describe the WBMRI pattern in a Brazilian cohort of LGMDR1 patients. The results showed that the involvement of paraspinal muscles, including the lumbar erector spinae, was more severe in these patients, with a striped appearance present in approximately 72% of them. There was a positive correlation between MRI scores and functional scores. The study suggests that WBMRI can provide a comprehensive evaluation of LGMDR1 patients and may be useful for diagnostic and outcome measure selection in clinical trials.
Review
Clinical Neurology
Duo-Zi Wang, Bing-Hu Li, Qiong Ma, Zhou Yu, Kai Chen, Ying He, Song Tan
Summary: This article reports a case of a 52-year-old woman with rare limb-girdle muscular dystrophy (LGMDR23), characterized by proximal weakness in the limbs. Magnetic resonance imaging (MRI) showed symmetrical sphenoid wings-like white matter demyelination in bilateral lateral ventricles. Electromyography revealed quadriceps muscle damage in both lower extremities. Next-generation sequencing (NGS) identified two loci variations in the LAMA2 gene. This case highlights the importance of considering LGMDR23 in patients with weakness and white matter demyelination on MRI brain, and expands the gene variants spectrum of LGMDR23.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Matthew Katz, Leigh B. Waddell, Michaela Yuen, Samantha J. Bryen, Emily Oates, Fleur C. Garton, Thomas Robertson, Robert David Henderson, Sandra T. Cooper, Pamela A. McCombe
Summary: This study reports two siblings with typical cerebral white matter changes and adult-onset limb girdle muscular dystrophy. They were found to have a previously unreported variant in the LAMA2 gene, expanding the genotypic and phenotypic spectrum of LGMDR23.
FRONTIERS IN NEUROLOGY
(2023)
Article
Oncology
Cheng Zhang, Xueping Zheng, Deguo Lu, Lulu Xu, Fengyuan Che, Shiguo Liu
Summary: A Chinese patient with limb-girdle muscular dystrophy recessive 1 was found to have compound heterozygous variants in the CAPN3 gene, expanding the variant spectrum of this gene. This discovery is important for improving the development of molecular diagnostic tools and providing genetic counseling for patients with a family history of the disease.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Medicine, General & Internal
Mark Richardson, Anna Mayhew, Robert Muni-Lofra, Lindsay B. Murphy, Volker Straub
Summary: The study aimed to determine the prevalence of pain in limb girdle muscular dystrophy R9 (LGMDR9) patients and its associations with genotypes, age, and ambulatory status. Findings showed that 87% of patients reported current pain, with 25% reporting severe current pain. The study concludes that pain should be considered a significant issue requiring management in individuals with LGMDR9.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Rheumatology
Italo Marago, Mark Roberts, Federico Roncaroli, Daniel DuPlessis, Caroline Sewry, Santhosh Nagaraju, Faheema Limbada, Chiara Marini-Bettolo, Judith Hudson, Siwalik Banerjee, Laura Newton, Marwan Bukhari, Hector Chinoy, James B. Lilleker
Summary: This study reviewed four patients initially misdiagnosed with IIM but later found to have LGMD 2 l, highlighting the importance of accurate diagnosis in differentiating non-inflammatory myopathies and avoiding inappropriate treatments. The patients had common features in clinical presentation, treatment response, and muscle imaging, emphasizing the need for clinicians to be aware of the potential mimicry of genetic myopathies in IIM diagnoses.
Article
Clinical Neurology
Xiuli Huang, Dandan Tan, Zaiqiang Zhang, Lin Ge, Jieyu Liu, Juan Ding, Haipo Yang, Cuijie Wei, Xingzhi Chang, Yun Yuan, Chuanzhu Yan, Hui Xiong
Summary: This study conducted a retrospective cross-sectional and longitudinal study on 19 Chinese patients with LAMA2-related limb girdle muscular dystrophy (LGMD R23), and found that most patients had normal early motor development, some had mild orthopedic complications, 36.8% had seizures, and 26.3% were diagnosed with epilepsy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. Missense variants in exon 4 may be correlated with epilepsy, and variants in the LN domain may be correlated with motor neuropathy. The study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Jorge Alonso-Perez, Lidia Gonzalez-Quereda, Claudio Bruno, Chiara Panicucci, Afagh Alavi, Shahriar Nafissi, Yalda Nilipour, Edmar Zanoteli, Lucas Michielon de Augusto Isihi, Bela Melegh, Kinga Hadzsiev, Nuria Muelas, Juan J. Vilchez, Mario Emilio Dourado, Naz Kadem, Gultekin Kutluk, Muhammad Umair, Muhammad Younus, Elena Pegorano, Luca Bello, Thomas O. Crawford, Xavier Suarez-Calvet, Ana Topf, Michela Guglieri, Chiara Marini-Bettolo, Pia Gallano, Volker Straub, Jordi Diaz-Manera
Summary: Sarcoglycanopathies are a group of genetic muscular diseases, with delta-sarcoglycanopathy being the rarest subtype. This study retrospectively analyzed a large cohort of delta-sarcoglycanopathy patients and found that the disease is severe and rapidly progressive, predominantly affecting limb muscles. Similar to other forms of sarcoglycanopathies, the abundance of protein on muscle biopsy inversely correlates with disease severity and progression rate.
Article
Biochemistry & Molecular Biology
Miguel Molina-Berenguer, Ferran Vila-Julia, Sandra Perez-Ramos, Maria Teresa Salcedo-Allende, Yolanda Camara, Javier Torres-Torronteras, Ramon Marti
Summary: Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 (COXPD1) is a mitochondrial translation disorder caused by mutations in GFM1. Mouse models with Gfm1 knock-in and knock-out mutations were generated to study COXPD1. The knock-in mice showed normal growth but had decreased mitochondrial EFG1 protein content, while the knock-out mice were embryonically lethal. The compound heterozygous mice had impaired mitochondrial translation and respiratory chain dysfunction, making them suitable for studying COXPD1.
Article
Medicine, General & Internal
Masanori Kurihara, Yusuke Sugiyama, Masaki Tanaka, Kenichiro Sato, Akihiko Mitsutake, Hiroyuki Ishiura, Akatsuki Kubota, Kaori Sakuishi, Toshihiro Hayashi, Atsushi Iwata, Jun Shimizu, Kei Murayama, Shoji Tsuji, Tatsushi Toda
Summary: Although aerobic exercise tests have been widely used for initial assessments of suspected mitochondrial disease cases, the test parameters for patients with final diagnoses of other diseases have not been fully characterized. Elevated venous peak lactate levels were observed in patients with final diagnoses of other diseases, even under a low 15-minute workload at 15 W. The lactate-to-pyruvate ratio and increase in lactate level from baseline may provide additional diagnostic value to venous peak lactate levels.
Article
Otorhinolaryngology
Kaoru Yamakawa, Hironobu Nishijima, Akatsuki Kubota, Hiroya Naruse, Shintaro Baba, Yoko Fujimaki, Kenji Kondo, Tatsushi Toda, Tatsuya Yamasoba
Summary: This case report describes a 70-year-old Japanese man with hereditary gelsolin amyloidosis (HGA) presenting with bilateral facial palsy. Genetic testing confirmed the diagnosis of HGA. Electrophysiological examinations revealed abnormal facial muscle activity and moderate bilateral upper facial nerve damage.
AURIS NASUS LARYNX
(2023)
Article
Clinical Neurology
Chiara Pizzamiglio, Robert D. S. Pitceathly, Michael P. Lunn, Stefen Brady, Fabiola De Marchi, Lucia Galan, Jeannine M. Heckmann, Alejandro Horga, Maria J. Molnar, Acary S. B. Oliveira, Wladimir B. V. R. Pinto, Guido Primiano, Ernestina Santos, Benedikt Schoser, Serenella Servidei, Paulo V. Sgobbi Souza, Vishnu Venugopalan, Michael G. Hanna, Mazen M. Dimachkie, Pedro M. Machado
Summary: Factors associated with the severity of COVID-19 outcomes in people with neuromuscular diseases (NMDs) include age, race/ethnicity, baseline functional status, comorbidities, history of respiratory dysfunction, obesity, number of comorbidities, glucocorticoid treatment, and Guillain-Barre syndrome.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Josep Gamez, Matilde Calopa, Esteban Munoz, Aileen Ferre, Oscar Huertas, Kevin McAllister, Nuria Reig, Catherine Scart-Gres, Raul Insa, Jaime Kulisevsky
Summary: The aim of this study was to investigate the efficacy and safety of SOM3355 as a repositioned treatment for reducing chorea in Huntington's disease. The results showed that SOM3355 reduced chorea in HD patients and was well-tolerated. Larger studies are needed to confirm its therapeutic utility as an antichoreic drug.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Keiko Hatano, Kenta Orimo, Mizuki Ogura, Shingo Okabe, Tadao Ishida, Akatsuki Kubota, Jun Shimizu, Hideji Hashida
Summary: A 36-year-old man developed POEMS syndrome after converting from solitary plasmacytoma of bone to multiple myeloma. He lost his independent walking ability 24 days after neurological onset. Treatment led to a reduction in serum VEGF level and subsequent regain of independent walking ability.
Review
Biochemistry & Molecular Biology
Elisenda Cortes-Saladelafont, Julian Fernandez-Martin, Saida Ortolano
Summary: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to dysfunctional lysosomal activity and the accumulation of specific substances in various organs. While research on central nervous system involvement in Fabry disease is limited, evidence suggests its clinical implications in conditions such as Parkinson's disease and neuropsychiatric disorders. This review aims to summarize the current scientific literature on these topics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Rheumatology
Naohiro Uchio, Shogo Komaki, Takashi Sudo, Yusuke Matsumoto, Akihito Hao, Kentaro Kojima, Nobuo Toda, Asuka Kitamura, Meiko Hashimoto Maeda, Akatsuki Kubota, Hideyuki Matsumoto
Summary: Gastrointestinal ulcers are a rare complication of dermatomyositis (DM) and occur less frequently in adults compared to juveniles. This case report presents a 50-year-old man with DM and anti-nuclear matrix protein 2 (anti-NXP2) antibodies who experienced relapsing multiple gastrointestinal ulcers. Despite treatment with prednisolone, the patient's muscle weakness and myalgia worsened and the ulcers recurred. However, intravenous immunoglobulin and azathioprine improved both his muscle weakness and gastrointestinal ulcers. The parallel disease activity of the muscular and gastrointestinal symptoms suggest that the ulcers were a complication of DM with anti-NXP2 antibodies. Early intensive immunosuppressive therapy should be considered for the management of muscular and gastrointestinal symptoms in DM with anti-NXP2 antibodies.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2023)
Meeting Abstract
Endocrinology & Metabolism
Saida Ortolano, Pedro Besada Pereira, Tania Perez, Marta Villar, Carmen Teran Moldes, Carlos Silva Lopez, Sergio Pantano, Ana Arevalo Gomez, Beatriz San Millan Tejado, Julian Fernandez-Martin
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Carlos Fernandez-Pereira, Maria Aranzazu Penedo, Tania Rivera-Baltanas, Tania Perez-Marquez, Marta Alves-Villar, Rafael Fernandez-Martinez, Cesar Veiga, Angel Salgado-Barreira, Jose Maria Prieto-Gonzalez, Saida Ortolano, Jose Manuel Olivares, Roberto Carlos Agis-Balboa
Summary: IGF-2 and IGFBP-7 levels are significantly increased in depressed patients, while levels of IGF-2, IGFBP-3, and IGFBP-5 are significantly decreased after antidepressant treatment, with IGFBP-7 showing a significant increase. This suggests that peripheral changes in the IGF family may reflect alterations at the brain level in depression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Luis G. Alcala-Gonzalez, Anna Accarino, Ramon Marti, Daniel Sanchez-Tejerina, Arnau Llaurado, Fernando Azpiroz, Carolina Malagelada
Summary: This study aims to describe gastrointestinal motor dysfunction in MNGIE patients using advanced techniques and evaluate the relationship between motor abnormalities and symptoms. The results show that MNGIE patients have characteristic motor dysfunction in the small bowel, even in the presence of mild digestive symptoms. Early investigation is necessary.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Article
Medicine, General & Internal
Beatriz San Millan-Tejado, Carmen Navarro, Julian Fernandez-Martin, Alberto Rivera, Irene Vieitez, Susana Teijeira, Saida Ortolano
Summary: Fabry disease is a rare lysosomal disorder caused by α-galactosidase A deficiency, resulting in systemic deposition of globotriasylceramide. Biopsy analyses revealed intralysosomal deposits in the skin, kidney, and endomyocardium of affected individuals. Treatment led to significant clearance of deposits in some cases.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Wolfgang Koehler, Marc Engelen, Florian Eichler, Robin Lachmann, Ali Fatemi, Jacinda Sampson, Ettore Salsano, Josep Gamez, Maria Judit Molnar, Silvia Pascual, Maria Rovira, Anna Vila, Guillem Pina, Itziar Martin-Ugarte, Adriana Mantilla, Pilar Pizcueta, Laura Rodriguez-Pascau, Estefania Traver, Anna Vilalta, Maria Pascual, Marc Martinell, Uwe Meya, Fanny Mochel
Summary: The effect of leriglitazone on disease progression in adult patients with adrenomyeloneuropathy was evaluated. The study found that leriglitazone did not significantly affect the change in the Six-Minute Walk Test distance, but it was generally well tolerated with adverse event rates in line with the expected safety profile for this drug class. Further investigation is needed to determine if leriglitazone can slow the progression of cerebral adrenoleukodystrophy.
Article
Public, Environmental & Occupational Health
J. Gamez, F. Carmona, A. Gamez, M. Santos
Summary: Pandemic fatigue led to a decrease in adherence to wearing masks outdoors in Barcelona during the sixth wave of the pandemic. Policymakers need to provide clear and enforceable guidelines to reduce the impact of fatigue on mask-wearing behavior.