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)
Review
Endocrinology & Metabolism
Randy J. Chandler, Charles P. Venditti
Summary: Organic acidemias (OA) are rare genetic metabolic disorders that cause the accumulation of organic acids in the body. Despite dietary and cofactor therapy, OA patients still face potentially life-threatening metabolic instability and long-term complications. Liver transplantation and gene therapy have been explored as potential treatments, with gene therapy experiments showing promise in mouse models of MMA and PA.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
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
Genetics & Heredity
Guang Ji, Yaling Liu, Xueqin Song, Zhenfei Li
Summary: In this study, two novel PCCB gene mutations were identified, suggesting the importance of considering late-onset propionic acidemia and conducting metabolic screening and gene analysis for a timely and definite diagnosis.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Kuntal Sen, Lindsay C. Burrage, Kimberly A. Chapman, Ilona Ginevic, George V. Mazariegos, Brett H. Graham
Summary: This statement serves as an educational resource for medical geneticists and clinicians, allowing them to provide quality medical services. Compliance with this statement is voluntary and does not guarantee a successful medical outcome. When determining the appropriateness of specific procedures or tests, clinicians should use their professional judgment based on the individual patient's circumstances. They are encouraged to document the reasons for using a particular procedure or test, whether or not it aligns with this statement. They should also consider the statement's adoption date and stay updated on new medical and scientific information, as well as any intellectual property restrictions on certain tests and procedures.
GENETICS IN MEDICINE
(2023)
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
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
Endocrinology & Metabolism
Sebastian Tims, Cyril Marsaux, Alex Pinto, Anne Daly, Daniela Karall, Mirjam Kuhn, Saikat Santra, Guus Roeselers, Jan Knol, Anita MacDonald, Sabine Scholl-Buergi
Summary: Propionic acidemia patients show differences in gut microbiota composition and metabolites compared to healthy controls, with increased Proteobacteria levels and decreased butyrate-producing genera. Patients exhibit lower diversity, stability, and butyrate production in their gut microbiota.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Medicine, General & Internal
Yao Chen, Xuehua Lin, Qingying Lin, Yinglin Zeng, Xiaolong Qiu, Guanghua Liu, Wenbin Zhu
Summary: This study focused on investigating potential pathogenic variants in the PCCA or PCCB gene in the Fujian Han population. The research identified compound heterozygous variants in the PCCB gene in two siblings from one family, with one novel missense variant found. Additionally, a novel missense variant in the PCCB gene was identified as a Variant of Undetermined Significance (VUS) for the first time in the Chinese population.
Article
Immunology
Maria Carmina Castiello, Martina Di Verniere, Elena Draghici, Elena Fontana, Sara Penna, Lucia Sereni, Alessandra Zecchillo, Denise Minuta, Paolo Uva, Marco Zahn, Irene Gil-Farina, Andrea Annoni, Silvia Iaia, Lisa M. Ott de Bruin, Luigi D. Notarangelo, Karin Pike-Overzet, Frank J. T. Staal, Anna Villa, Valentina Capo
Summary: This study evaluated the efficacy of gene therapy in hypomorphic RAG1 mouse models and found that it has the potential to partially alleviate the immune deficiency in these patients. However, further research is needed before commencing RAG gene therapy in these highly complex patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sinziana Stanescu, Amaya Belanger-Quintana, Borja Manuel Fernandez-Felix, Pedro Ruiz-Sala, Mercedes del Valle, Fernando Garcia, Francisco Arrieta, Mercedes Martinez-Pardo
Summary: This study investigates the amino acid profiles of patients with propionic acidemia, finding that deficiency of propionyl-CoA and its precursors during metabolic decompensation may result in impaired synthesis of urea cycle amino acids and ammonia detoxification.
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
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
Multidisciplinary Sciences
Karl-Heinz Tomaszowski, Sunetra Roy, Carolina Guerrero, Poojan Shukla, Caezaan Keshvani, Yue Chen, Martina Ott, Xiaogang Wu, Jianhua Zhang, Courtney D. DiNardo, Detlev Schindler, Katharina Schlacher
Summary: This study reveals that Fanconi anemia patients frequently have mutations in multiple FANC genes. In a mouse model, simultaneous mutations in Brca2/Fancd1 and Rad51c/Fanco genes can replicate the phenotypes of human Fanconi anemia, including bone marrow failure, cancer susceptibility, hypersensitivity to cancer drugs, and severe replication instability. This research has important implications for a better understanding of the role of FANC genes in tumorigenesis.
NATURE COMMUNICATIONS
(2023)
Review
Genetics & Heredity
Yingxuan Li, Miaomiao Wang, Zhaoyang Huang, Jing Ye, Yuping Wang
Summary: This report describes a case of propionic acidemia (PA) with an adult-onset phenotype and a novel compound heterozygous mutation in the PCCB gene. Patients carrying mutations in the PCCB gene tend to develop late-onset PA and present neuropsychiatric symptoms and/or signs. Further molecular biological research is needed to explore the genotype-phenotype correlations of PA.
BMC MEDICAL GENOMICS
(2022)
