Article
Genetics & Heredity
Flavia Tubili, Francesca Pochiero, Maria Rosaria Curcio, Elena Procopio
Summary: This study describes a case of a child with MMA who was successfully managed using CA adjunctive therapy and dietary adjustments, resulting in controlled ammonium levels and normal growth.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Endocrinology & Metabolism
Allison J. Armstrong, Maria Sol Collado, Brad R. Henke, Matthew W. Olson, Stephen A. Hoang, Christin A. Hamilton, Taylor D. Pourtaheri, Kimberly A. Chapman, Marshall M. Summar, Brian A. Johns, Brian R. Wamhoff, John E. Reardon, Robert A. Figler
Summary: Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) are inborn errors of metabolism causing the accumulation of propionyl-coenzyme A (P-CoA) and methylmalonyl-CoA (M-CoA). A small molecule therapy, HST5040, showed reduction in disease-relevant biomarkers in liver cell-based models using patient-derived primary hepatocytes.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Genetics & Heredity
Majid Alfadhel, Marwan Nashabat, Mohammed Saleh, Mohammed Elamin, Ahmed Alfares, Ali Al Othaim, Muhammad Umair, Hind Ahmed, Faroug Ababneh, Fuad Al Mutairi, Wafaa Eyaid, Abdulrahman Alswaid, Lina Alohali, Eissa Faqeih, Mohammed Almannai, Majed Aljeraisy, Bayan Albdah, Mohamed A. Hussein, Zuhair Rahbeeni, Ali Alasmari
Summary: The study evaluated the effectiveness of administering carglumic acid with standard treatment compared to standard treatment alone in managing propionic acidemia (PA) and methylmalonic acidemia (MMA). Results showed that using carglumic acid in addition to standard treatment significantly reduced the number of emergency room admissions due to hyperammonemia in patients with PA and MMA. The primary efficacy endpoint demonstrated a significant difference in ER admissions between the carglumic acid arm and standard treatment alone.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
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
Medical Laboratory Technology
Mengmeng Du, Shengnan Wu, Chang Su, Xiaohong Wang, Bingbing Li, Yifan Lin, Shuxian Yuan, Yongxing Chen, Changlian Zhu, Haiyan Wei
Summary: This study investigated whether serum Vitamin B12 levels could be used as an early diagnostic biomarker for MMA. The results showed that serum Vitamin B12 levels were significantly increased in MMA patients, and serum Vitamin B12 combined with other biomarkers could be used to distinguish different types of MMA. Additionally, elevated Vitamin B12 was found to be an independent predictor of MMA clinical onset.
CLINICA CHIMICA ACTA
(2023)
Article
Cell & Tissue Engineering
Jing Luan, Hui Zou, Yazhou Cui, Jing Wang, Zhenzhong Han, Genglin Zhang, Jinxiang Han
Summary: Methylmalonic acidemia (MMA) is a hereditary disease caused by a defect in methylmalonyl-CoA mutase or cobalamin metabolism. Mutations in the MMACHC gene lead to metabolic disorder and the accumulation of methylmalonic acid, resulting in organ dysfunction. Researchers generated induced pluripotent stem cells (iPSCs) from a MMA patient and created a cellular model for studying the disease.
STEM CELL RESEARCH
(2022)
Article
Genetics & Heredity
Sonia Pajares, Jose Antonio Arranz, Aida Ormazabal, Mireia Del Toro, Angeles Garcia-Cazorla, Aleix Navarro-Sastre, Rosa Maria Lopez, Silvia Maria Meavilla, Mariela Mercedes de los Santos, Camila Garcia-Volpe, Jose Manuel Gonzalez de Aledo-Castillo, Ana Argudo, Jose Luis Marin, Clara Carnicer, Rafael Artuch, Frederic Tort, Laura Gort, Rosa Fernandez, Judit Garcia-Villoria, Antonia Ribes
Summary: The study aimed to assess the utility of a second-tier test in newborn screening, finding that levels of MMA and Hcys were higher in acquired vitamin B-12 deficiency, while MCA was mainly present in genetic disorders.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Fereshteh Maryami, Elham Rismani, Elham Davoudi-Dehaghani, Nasrin Khalesi, Fatemeh Zafarghandi Motlagh, Alireza Kordafshari, Saeed Talebi, Hamzeh Rahimi, Sirous Zeinali
Summary: This study identifies a new pathogenic variant in the MMAB gene that is responsible for severe MMA and neonatal death. The variant affects the structure and function of the protein, expanding the variant spectra of MMAB. These findings have important implications for prenatal diagnosis of MMA and carrier screening of family members.
Article
Medicine, General & Internal
Yunting Pang, Fanqing Meng, Yaqiu Guo, Feng Zhou
Summary: Methylmalonic acidemia (MMA) combined with hyperhomocysteinemia is an autosomal recessive genetic disease that can cause metabolic acidosis, elevated lactate, and high blood ammonia level. The main focus of anesthetic management is to maintain the stable state of perioperative physiological metabolism in such patients. This case involves a patient with comitant esotropia and methylmalonic acidemia combined with hyperhomocysteinemia.
CLINICAL CASE REPORTS
(2023)
Review
Pediatrics
Alessia Marcellino, Cristiana Alessia Guido, Silvia Bloise, Saverio Mallardo, Sara Isoldi, Emanuela Del Giudice, Anna Dilillo, Vanessa Martucci, Mariateresa Sanseviero, Donatella Iorfida, Alberto Spalice, Riccardo Lubrano
Summary: Research has shown that children of methylmalonic acidemia patients may have neurological developmental defects, highlighting the need for physicians to pay attention to their growth and neurological examinations.
Article
Genetics & Heredity
Lili Liang, Ruixue Shuai, Yue Yu, Wenjuan Qiu, Linghua Shen, Shengnan Wu, Haiyan Wei, Yongxing Chen, Chiju Yang, Peng Xu, Xigui Chen, Hui Zou, Jizhen Feng, Tingting Niu, Haili Hu, Jun Ye, Huiwen Zhang, Deyun Lu, Zhuwen Gong, Xia Zhan, Wenjun Ji, Yongguo Yu, Xuefan Gu, Lianshu Han
Summary: Patients with the c.1663G > A (p.A555T) mutation in the MMUT gene showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis compared to patients with other mutations in the MMUT gene. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Yue Yu, Ruixue Shuai, Lili Liang, Wenjuan Qiu, Linghua Shen, Shengnan Wu, Haiyan Wei, Yongxing Chen, Chiju Yang, Peng Xu, Xigui Chen, Hui Zou, Jizhen Feng, Tingting Niu, Haili Hu, Jun Ye, Huiwen Zhang, Deyun Lu, Zhuwen Gong, Xia Zhan, Wenjun Ji, Xuefan Gu, Lianshu Han
Summary: The study found that different mutations in the MMUT gene are associated with the response to vitamin B12 treatment and also have an impact on the outcomes of healthy/developmental delay.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Obstetrics & Gynecology
Lizi Jin, Xueyan Han, Falin He, Chuanbao Zhang
Summary: The study estimated the global prevalence of MMA, revealing a low prevalence among newborns but higher among the clinical-suspected population, with Asia and Africa showing higher rates. It recommended improvements in newborn screening strategies and closer monitoring of high-risk populations.
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
(2022)
Article
Biochemical Research Methods
Johanna Piibor, Andres Waldmann, Keerthie Dissanayake, Aneta Andronowska, Marilin Ivask, Madhusha Prasadani, Ants Kavak, Suranga Kodithuwakku, Alireza Fazeli
Summary: This study used quantitative proteomics-based mass spectrometry to investigate the changes in the proteome of extracellular vesicles (EVs) in the uterine fluid (UF) during the bovine estrous cycle. The results showed that the UF-EV proteome is cycle-dependent and differentially enriched proteins play important roles in normal uterine functions and early embryo development. Furthermore, supplementation of UF-EVs during the luteal phase increased embryo production in vitro. These findings highlight the importance of UF-EVs in uterine communications and their potential use in improving embryo production.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Biochemical Research Methods
Kevin Dick, Arezo Pattang, Julia Hooker, Nour Nissan, Michael Sadowski, Bradley Barnes, Le Hoa Tan, Daniel Burnside, Sadhna Phanse, Hiroyuki Aoki, Mohan Babu, Frank Dehne, Ashkan Golshani, Elroy R. Cober, James R. Green, Bahram Samanfar
Summary: By analyzing the protein-protein interaction network between humans and soybeans, potential important proteins related to human health and putative allergens can be identified. The study leverages advanced PPI predictors to predict interactions between humans and soybeans, exploring proteins related to immune and neurological pathways.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Emanuela Marchese, Marianna Caterino, Roberta Fedele, Francesca Pirozzi, Armando Cevenini, Neha Gupta, Diego Ingrosso, Alessandra Perna, Giovambattista Capasso, Margherita Ruoppolo, Miriam Zacchia
Summary: This study provides insights into the mechanisms underlying renal disease in Bardet-Biedl syndrome (BBS) through urine metabolomic and proteomic analyses. The increased urinary excretion of lactate suggests a possible renal-specific defective handling. The BBS10 gene may play a role in renal metabolism, RNA processing, and cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Iolanda Boffa, Elena Polishchuk, Lucia De Stefano, Fabio Dell'Aquila, Edoardo Nusco, Elena Marrocco, Matteo Audano, Silvia Pedretti, Marianna Caterino, Ilaria Bellezza, Margherita Ruoppolo, Nico Mitro, Barbara Cellini, Alberto Auricchio, Nicola Brunetti-Pierri
Summary: GACR is a chorioretinal degeneration caused by pathogenic variants in the gene encoding ornithine aminotransferase (OAT). The current therapies are unsatisfactory and this study investigates the efficacy of liver-directed AAV-mediated gene therapy using an intravenously injected AAV8 vector expressing OAT. The results show that this gene therapy effectively reduces ornithine concentrations and improves retinal function and structure in mouse models of OAT deficiency.
EMBO MOLECULAR MEDICINE
(2023)
Article
Genetics & Heredity
Kerri Bosfield, Jessica Albert, Nancy Cheng, Tiffany Swaringer, Kristina Cusmano-Ozog, Debra S. Regier
Summary: The purpose of this study was to standardize the learning experience in a biochemical genetics laboratory rotation. The revised rotation included various teaching modalities and was well received by trainees and faculty. The learners' learning outcomes improved significantly, and they were able to interact with laboratory staff more effectively.
GENETICS IN MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Richa Madan Lomash, Oleg J. Shchelochkov, Randy P. Chandler, Charles A. Venditti, Anne Pariser, Elizabeth Ottinger
Summary: The Orphan Drug Designation (ODD) program in the United States facilitates the development of drugs for rare diseases, including pediatric patients. A gene therapy program called Platform Vector Gene Therapy (PaVe-GT) was initiated in 2019 to develop gene therapies for rare disorders. The program obtained ODD and RPDD for an adeno-associated virus gene therapy to treat propionic acidemia.
HUMAN GENE THERAPY
(2023)
Article
Multidisciplinary Sciences
Marianna Caterino, Roberta Fedele, Vincenzo Carnovale, Alice Castaldo, Monica Gelzo, Paola Iacotucci, Margherita Ruoppolo, Giuseppe Castaldo
Summary: Cystic fibrosis is a hereditary metabolic disorder affecting chloride ions and water transport, resulting in inadequate hydration and dehydrated secretions. Understanding the metabolic alterations associated with the disease can help in developing targeted therapeutic strategies. This study used mass spectrometry analysis to investigate lipid metabolic changes in saliva samples from CF patients, associated with various complications.
SCIENTIFIC REPORTS
(2023)
Article
Environmental Sciences
Stefania Orru, Esther Imperlini, Daniela Vitucci, Marianna Caterino, Annalisa Mandola, Morten Bredsgaard Randers, Jakob Friis Schmidt, Marie Hagman, Thomas Rostgaard Andersen, Peter Krustrup, Margherita Ruoppolo, Pasqualina Buono, Annamaria Mancini
Summary: Lifelong football training has a positive impact on the oxidative capacity and body composition of elderly individuals, promoting successful aging. Furthermore, polyamines play an important role in muscle growth and hypertrophy.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Genetics & Heredity
Annie D. D. Niehaus, Bryce A. A. Mendelsohn, Bree Zimmerman, Chung U. U. Lee, Melanie A. A. Manning, Kristina P. P. Cusmano-Ozog, Christina G. G. Tise
Summary: We report three individuals who were exposed to maternal autoantibodies during pregnancy and had elevated VLCFAs in the newborn period after screening positive for ALD. Two of them showed clinical and laboratory features of NLE, while the third had features suggestive of NLE as well as a maternal history of Sjogren's syndrome and rheumatoid arthritis. Subsequent evaluation for peroxisomal disorders was nondiagnostic, and the VLCFAs normalized by 15 months of age. These cases contribute to the expanding differential diagnosis for newborns with elevated C26:0-lysophosphatidylcholine due to ALD screening.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Christina G. Tise, Courtney P. Verscaj, Bryce A. Mendelsohn, Jeremy Woods, Chung U. Lee, Gregory M. Enns, Zinandre Stander, Patricia L. Hall, Tina M. Cowan, Kristina P. Cusmano-Ozog
Summary: Low citrulline in newborn screening can be used to identify various mitochondrial diseases. This study found that infants with low citrulline were ultimately diagnosed with MT-ATP6 mitochondrial disease. By comparing with reference data, it is possible to effectively distinguish other types of diseases.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Carolina I. Galarreta, Karen Wong, Jason Carmichael, Jeremy Woods, Christina G. Tise, Annie D. Niehaus, Alison J. Schildt, Courtney P. Verscaj, Kristina P. Cusmano-Ozog
Summary: Zellweger spectrum disorder (ZSD) is a group of autosomal recessive disorders caused by biallelic pathogenic variants in any one of the 13 PEX genes essential for peroxisomal biogenesis. We report a cohort of nine infants who presented at birth with severe neonatal features suggestive of ZSD and found to be homozygous for a variant in PEX6 (NM_000287.4:c.1409G > C[p.Gly470Ala]). Gly470Ala may represent a founder variant in the Mixtec population of Central California. ZSD should be considered in patients who present at birth with severe hypotonia and enlarged fontanelles, especially in the setting of an abnormal NBS, Mixtec ancestry, or family history of infant death. There is a need to further characterize the natural history of ZSD, the Gly470Ala variant, and expand upon possible genotype-phenotype correlations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Ferdinando Barretta, Fabiana Uomo, Simona Fecarotta, Lucia Albano, Daniela Crisci, Alessandra Verde, Maria Grazia Fisco, Giovanna Gallo, Daniela Dottore Stagna, Maria Rosaria Pricolo, Marianna Alagia, Gaetano Terrone, Alessandro Rossi, Giancarlo Parenti, Margherita Ruoppolo, Cristina Mazzaccara, Giulia Frisso
Summary: This study reports the diagnostic yield of genetic testing for MTHFR deficiency diagnosis in a reference Centre of Southern Italy between 2017 and 2022. The results showed that two NBS-positive newborns and one symptomatic patient had a genotype compatible with MTHFR deficiency. These findings strongly support the need for genetic testing to quickly support the definitive diagnosis of MTHFR deficiency and start therapy.
Editorial Material
Medicine, Research & Experimental
Randy J. Chandler
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(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
Ilaria Campesi, Giampiero Capobianco, Antonella Cano, Valeria Lodde, Sara Cruciani, Margherita Maioli, Giovanni Sotgiu, Maria Laura Idda, Mariangela Valentina Puci, Margherita Ruoppolo, Michele Costanzo, Marianna Caterino, Francesca Cambosu, Andrea Montella, Flavia Franconi
Summary: This study found sex-related differences in amniotic fluid and amniotic fluid cells. Inflammation markers and certain metabolites were higher in female amniotic fluid, while other metabolites were higher in male amniotic fluid. Female amniotic fluid cells expressed more estrogen receptors and proteins associated with autophagy, while male amniotic fluid cells expressed more proteins associated with lysosomes.
Article
Medicine, General & Internal
Christina G. Tise, Melinda J. Palma, Kristina P. Cusmano-Ozog, Dena R. Matalon
Summary: Cerebral creatine deficiency syndromes (CCDS) are a rare group of inherited metabolic disorders that present with nonspecific symptoms. Creatine transporter (CRTR) deficiency is the most common CCDS, with X-linked inheritance. This case report describes a 20-month-old boy with failure to thrive (FTT) and abnormal neurodevelopmental features. He was diagnosed with CRTR deficiency based on low serum creatinine levels, elevated urine creatine, and a family history of learning disabilities and developmental delay. Early diagnosis and intervention are important for affected individuals, as there are existing therapies for CCDS.
JOURNAL OF INVESTIGATIVE MEDICINE HIGH IMPACT CASE REPORTS
(2023)