Article
Genetics & Heredity
Yi Liu, Zhehui Chen, Hui Dong, Yuan Ding, Ruxuan He, Lulu Kang, Dongxiao Li, Ming Shen, Ying Jin, Yao Zhang, Jinqing Song, Yaping Tian, Yongtong Cao, Desheng Liang, Yanling Yang
Summary: This study investigated the clinical features, outcomes, molecular epidemiology, and phenotype-genotype relationship in Chinese patients with propionic acidemia. The results showed that neurological abnormalities were the most frequent complications of propionic acidemia, and newborn screening can help detect the disease early. Certain variants with high frequencies and homozygotes may be associated with early-onset or late-onset propionic acidemia.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Zhi-Gui Zeng, Guang-Peng Zhou, Lin Wei, Wei Qu, Ying Liu, Yu-Le Tan, Jun Wang, Li-Ying Sun, Zhi-Jun Zhu
Summary: This study evaluates the clinical outcomes of living donor liver transplantation (LDLT) in children with propionic acidemia (PA), using obligate heterozygous carriers as donors. The results show that all patients had a successful transplantation with no severe complications, and the living donors also recovered well with no complications. The study suggests that LDLT using partial liver grafts from asymptomatic obligate heterozygous carriers is a viable treatment option for selected PA patients.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Pharmacology & Pharmacy
Hannah Marchuk, You Wang, Zachary Alec Ladd, Xiaoxin Chen, Guo-Fang Zhang
Summary: Propionic acidemia (PA) is a genetic metabolic disorder caused by mutations in the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), leading to the accumulation of propionyl-CoA and its metabolites. This accumulation can result in various complications, including life-threatening cardiac diseases and metabolic strokes. The pathophysiological mechanisms underlying these complications are not fully understood, but research suggests that impaired mitochondrial energy metabolism and oxidative stress play a role. Further investigation into these mechanisms can lead to more effective therapeutic treatments for PA.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Clinical Neurology
Ling-Xiao Cao, Wen-Zheng Hu, Wei Dong, Qing Yang, Jin-Hui Yin, Yue Wang, Xin Ni, Yue Huang
Summary: Propionic acidemia is a autosomal recessive metabolic disease that affects multiple systems of the human body. This study reports neuropathological findings in a patient with propionic acidemia. The patient presented with symptoms shortly after birth and died after complications from a liver transplantation. Postmortem examination revealed significant pathological changes in the brain.
Article
Biochemistry & Molecular Biology
Husain Attarwala, Matthew Lumley, Min Liang, Vijay Ivaturi, Joe Senn
Summary: A translational semimechanistic pharmacokinetic (PK) and PK/pharmacodynamic (PD) model was developed to quantify the relationship between the mRNA components of mRNA-3927 (an LNP encapsulating PCCA and PCCB mRNAs) and dose levels, guiding the selection of dose range and regimen for the Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT04159103) in adult and pediatric patients with PA.
NUCLEIC ACID THERAPEUTICS
(2023)
Article
Biology
Ali Al-Asmari, Abdul Ali Peer-Zada, Abdulwahed AlDehaimi, Constantin Polychronakos, Aziz A. Chentoufi
Summary: The aim of this study is to develop a rapid and effective method for screening Saudi carriers of the most common propionic acidemia mutation (c.425G > A) and studying the functional impact of this mutation. Using allele-specific primers, the researchers have developed a qPCR assay that accurately distinguishes heterozygotes from mutated and wild type homozygotes.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Endocrinology & Metabolism
Chitra Subramanian, Matthew W. Frank, Rajendra Tangallapally, Mi-Kyung Yun, Stephen W. White, Richard E. Lee, Charles O. Rock, Suzanne Jackowski
Summary: The study demonstrates that BBP-671 can correct metabolic imbalances, improve mitochondrial function, reduce plasma PA biomarkers, and extend the lifespan of PA mice.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Medicine, General & Internal
Sobia Irum, Ambreen Rehman, Muhammad Aamir, Zujaja Hina Haroon, Nayyar Chaudhry, Afshan Bibi
Summary: Propionic Acidemia (PA) is a rare metabolic disorder that can be diagnosed based on clinical symptoms and laboratory tests.
JCPSP-JOURNAL OF THE COLLEGE OF PHYSICIANS AND SURGEONS PAKISTAN
(2022)
Article
Endocrinology & Metabolism
Wentao He, You Wang, Erik J. Xie, Michael A. Barry, Guo-Fang Zhang
Summary: Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by mutations in genes encoding propionyl-CoA carboxylase, resulting in various complications. Investigation of Pcca(-/-)(A138T) mice under different dietary conditions can provide insights into the pathological mechanisms of PA. Organ-specific metabolic alterations under varying severities of PA were observed, shedding light on the disease progression.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Microbiology
Jin Feng, Maurice Hauser, Russell J. Cox, Elizabeth Skellam
Summary: The study demonstrated the modification of Aspergillus oryzae metabolism for the synthesis of triketide lactone, indicating it as an alternative host for producing polyketides from bacteria, potentially offering advantages over current heterologous platforms.
Article
Microbiology
Pan Wang, Xin Wang, Ying Yin, Mingliang He, Wei Tan, Wenting Gao, Jianping Wen
Summary: The study found that inactivating the signal transduction protein GlnB can increase the production of ascomycin by enhancing the supply of precursors. Protein co-precipitation experiments and coupled enzyme activity assays revealed that the interaction between GlnB protein and the alpha subunit of acetyl-CoA carboxylase and propionyl-CoA carboxylase inhibited their activities.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Florian Malard, Cameron D. Mackereth, Sebastien Campagne
Summary: This article discusses the early stage of spliceosome assembly in eukaryotes, focusing on the factors that influence U1 snRNP's selection of splice sites in pre-mRNA. It also includes examples of diseases that affect this selection and recent therapeutic advances.
Article
Medicine, General & Internal
Adina Neumann, Miguel Angel Alcantara-Ortigoza, Ariadna Gonzalez-Del Angel, Nestor Alejandro Zarate Diaz, Javier Sam Santana, Leonardo M. Porchia, Esther Lopez-Bayghen
Summary: This study demonstrates the successful application of a low-cost preimplantation genetic testing approach for detecting propionic acidemia, resulting in the birth of a healthy newborn by reducing the transmission of a pathogenic variant of the PCCA gene.
WORLD JOURNAL OF CLINICAL CASES
(2021)
Article
Medicine, Research & Experimental
Randy J. Chandler, Giovanni Di Pasquale, Eun-Young Choi, David Chang, Stephanie N. Smith, Jennifer L. Sloan, Victoria Hoffmann, Lina Li, John A. Chiorini, Charles P. Venditti
Summary: In this study, the therapeutic efficacy of AAV44.9 vector in treating propionic acidemia (PA) was evaluated using a new mouse model. The results showed that a single injection of AAV44.9 vector at birth improved survival, reduced plasma methylcitrate, and resulted in high levels of transgene expression in the liver and heart. These findings suggest the potential of AAV44.9 vector for the treatment of metabolic disorders.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Endocrinology & Metabolism
Najla Albader, Minjing Zou, Huda A. BinEssa, Saba Abdi, Anwar F. Al-Enezi, Brian F. Meyer, Ali S. Alzahrani, Yufei Shi
Summary: The study evaluated the impact of noncanonical splice-site variants on pre-mRNA splicing in CH-causing genes, identifying some variants that lead to aberrant splicing and others that have no effect on RNA splicing. The variant-prediction program CADD demonstrated the highest accuracy in predicting noncanonical splice-site variants.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Rosa Navarrete, Fatima Leal, Ana Vega, Ana Morais-Lopez, Maria Teresa Garcia-Silva, Elena Martin-Hernandez, Pilar Quijada-Fraile, Ana Bergua, Inmaculada Vives, Inmaculada Garcia-Jimenez, Raquel Yahyaoui, Consuelo Pedron-Giner, Amaya Belanger-Quintana, Sinziana Stanescu, Elvira Canedo, Oscar Garcia-Campos, Maria Bueno-Delgado, Carmen Delgado-Pecellin, Isidro Vitoria, Maria Dolores Rausell, Elena Balmaseda, Mari Luz Couce, Lourdes R. Desviat, Begona Merinero, Pilar Rodriguez-Pombo, Magdalena Ugarte, Celia Perez-Cerda, Belen Perez
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)
Article
Cell & Tissue Engineering
Aristides Lopez-Marquez, Esmeralda Alonso-Barroso, Gema Cerro-Tello, Irene Bravo-Alonso, Laura Arribas-Carreira, Alvaro Briso-Montiano, Rosa Navarrete, Celia Perez-Cerda, Magdalena Ugarte, Belen Perez, Lourdes R. Desviat, Eva Richard
STEM CELL RESEARCH
(2019)
Letter
Clinical Neurology
Lourdes R. Desviat, Cecilia Jimenez Mallebrera, Ainara Vallejo-Illarramendi, Maria D. Mayan, Gisela Nogales-Gadea, Virginia Arechavala-Gomeza
Article
Medicine, General & Internal
Irene Bravo-Alonso, Rosa Navarrete, Ana Isabel Vega, Pedro Ruiz-Sala, Maria Teresa Garcia Silva, Elena Martin-Hernandez, Pilar Quijada-Fraile, Amaya Belanger-Quintana, Sinziana Stanescu, Maria Bueno, Isidro Vitoria, Laura Toledo, Maria Luz Couce, Inmaculada Garcia-Jimenez, Ricardo Ramos-Ruiz, Miguel Angel Martin, Lourdes R. Desviat, Magdalena Ugarte, Celia Perez-Cerda, Begona Merinero, Belen Perez, Pilar Rodriguez-Pombo
JOURNAL OF CLINICAL MEDICINE
(2019)
Article
Biochemistry & Molecular Biology
M. Tamayo, A. Fulgencio-Covian, J. A. Navarro-Garcia, A. Val-Blasco, G. Ruiz-Hurtado, M. Gil-Fernandez, L. Martin-Nunes, J. A. Lopez, L. R. Desviat, C. Delgado, E. Richard, M. Fernandez-Velasco
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2020)
Article
Genetics & Heredity
Diana Gallego, Fatima Leal, Alejandra Gamez, Margarita Castro, Rosa Navarrete, Obdulia Sanchez-Lijarcio, Isidro Vitoria, Maria Bueno-Delgado, Amaya Belanger-Quintana, Ana Morais, Consuelo Pedron-Giner, Inmaculada Garcia, Jaume Campistol, Rafael Artuch, Carlos Alcaide, Veronica Cornejo, David Gil, Raquel Yahyaoui, Lourdes R. Desviat, Magdalena Ugarte, Aurora Martinez, Belen Perez
Article
Medical Laboratory Technology
Alejandro Fulgencio-Covian, Esmeralda Alonso-Barroso, Adam J. Guenzel, Ana Rivera-Barahona, Magdalena Ugarte, Belen Perez, Michael A. Barry, Celia Perez-Cerda, Eva Richard, Lourdes R. Desviat
TRANSLATIONAL RESEARCH
(2020)
Article
Genetics & Heredity
Alicia Hillert, Yair Anikster, Amaya Belanger-Quintana, Alberto Burlina, Barbara K. Burton, Carla Carducci, Ana E. Chiesa, John Christodoulou, Maja Dordevic, Lourdes R. Desviat, Aviva Eliyahu, Roeland A. F. Evers, Lena Fajkusova, Francois Feillet, Pedro E. Bonfim-Freitas, Maria Gizewska, Polina Gundorova, Daniela Karall, Katya Kneller, Sergey Kutsev, Vincenzo Leuzzi, Harvey L. Levy, Uta Lichter-Konecki, Ania C. Muntau, Fares Namour, Mariusz Oltarzewski, Andrea Paras, Belen Perez, Emil Polak, Alexander Polyakov, Francesco Porta, Marianne Rohrbach, Sabine Scholl-Burgi, Norma Specola, Maja Stojiljkovic, Nan Shen, Luiz C. Santana-da Silva, Anastasia Skouma, Francjan van Spronsen, Vera Stoppioni, Beat Thony, Friedrich K. Trefz, Jerry Vockley, Youngguo Yu, Johannes Zschocke, Georg F. Hoffmann, Sven F. Garbade, Nenad Blau
AMERICAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Biochemistry & Molecular Biology
A. Vilas, P. Yuste-Checa, D. Gallego, L. R. Desviat, M. Ugarte, C. Perez-Cerda, A. Gamez, B. Perez
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Esmeralda Alonso-Barroso, Belen Perez, Lourdes Ruiz Desviat, Eva Richard
Summary: Propionic acidemia (PA) is a common life-threatening organic acidemia caused by mutations in PCCA or PCCB genes. Cardiac alterations are a major cause of mortality in PA patients. Study using iPSC derived cardiomyocytes from a PA patient showed characteristics such as reduced oxygen consumption and endoplasmic reticulum stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Alejandro Fulgencio-Covian, Mar Alvarez, Barry A. Pepers, Aristides Lopez-Marquez, Magdalena Ugarte, Belen Perez, Willeke M. C. van Roon-Mom, Lourdes R. Desviat, Eva Richard
STEM CELL RESEARCH
(2020)
Review
Cardiac & Cardiovascular Systems
Kyung Chan Park, Steve Krywawych, Eva Richard, Lourdes R. Desviat, Pawel Swietach
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2020)
Review
Medicine, Research & Experimental
Suzan M. Hammond, Annemieke Aartsma-Rus, Sandra Alves, Sven E. Borgos, Ronald A. M. Buijsen, Rob W. J. Collin, Giuseppina Covello, Michela A. Denti, Lourdes R. Desviat, Lucia Echevarria, Camilla Foged, Gisela Gaina, Alejandro Garanto, Aurelie T. Goyenvalle, Magdalena Guzowska, Irina Holodnuka, David R. Jones, Sabine Krause, Taavi Lehto, Marisol Montolio, Willeke Van Roon-Mom, Virginia Arechavala-Gomeza
Summary: The field of nucleic acid-based therapeutics has seen rapid development in recent years, with the main challenge being delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ainhoa Martinez-Pizarro, Fatima Leal, Lise Lolle Holm, Thomas K. Doktor, Ulrika S. S. Petersen, Maria Bueno, Beat Thony, Belen Perez, Brage S. Andresen, Lourdes R. Desviat
Summary: We report the identification of two new splicing variants of 6-pyruvoyl-tetrahydropterin synthase in a patient with tetrahydrobiopterin deficiency. These variants were found to cause the inclusion of abnormal pseudoexons, leading to hyperphenylalaninemia and monoamine neurotransmitter deficiency. Antisense oligonucleotides were designed to correct the aberrant pseudoexon inclusion, demonstrating the therapeutic potential of this approach.
NUCLEIC ACID THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Mar Alvarez, Pedro Ruiz-Sala, Belen Perez, Lourdes Ruiz Desviat, Eva Richard
Summary: Propionic acidemia (PA) disorder primarily affects the heart and leads to cardiac complications due to the accumulation of toxic metabolites. Cardiomyocytes generated from induced pluripotent stem cells (iPSCs) derived from a PA patient were used to study microRNAs (miRNAs) profiles and cellular pathways associated with PA cardiac phenotypes. The study identified upregulated cardiac-enriched miRNAs and alterations in various cellular pathways, providing insights into the molecular mechanisms of this rare disease and potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)