Article
Medicine, General & Internal
Li-Ping Wang, Hou-Zhong Luo, Mao Song, Zuo-Zhen Yang, Fan Yang, Yun-Tao Cao, Juan Chen
Summary: This study identified a novel variant in the OTC gene and validated related clinical features, which can serve as references for further OTCD screening and clinical consultation.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Endocrinology & Metabolism
Stephanie Gobin-Limballe, Chris Ottolenghi, Fabien Reyal, Jean-Baptiste Arnoux, Maryse Magen, Marie Simon, Anais Brassier, Fabienne Jabot-Hanin, Pascale De Lonlay, Clement Pontoizeau, Manel Guirat, Marlene Rio, Roselyne Gesny, Nadine Gigarel, Ghislaine Royer, Julie Steffann, Arnold Munnich, Jean-Paul Bonnefont
Summary: This study on females in OTC deficient families found that 22% of heterozygous females were clinically affected, with a higher risk of severe disease in females with severe mutations. Variability in OTC activity and X inactivation profile within the liver was observed, with little correlation between the two in most cases.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Cell & Tissue Engineering
Jingyun Guan, Beibei Yan, Haiyan Zhang, Chen Liu, Yue Li, Xiaomeng Yang, Zilong Li, Zhongtao Gai, Yi Liu
Summary: Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked urea cycle disorder that can lead to life-threatening hyperammonemia if untreated. By generating an iPSC line from a patient with OTCD, researchers were able to create a model for exploring the pathogenesis and therapy of OTCD, as the iPSC line showed normal karyotype, pluripotency, and potential to differentiate into three germ layers.
STEM CELL RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Ioannis A. Ziogas, W. Kelly Wu, Lea K. Matsuoka, Anita K. Pai, Einar T. Hafberg, Lynette A. Gillis, Thomas M. Morgan, Sophoclis P. Alexopoulos
Summary: Liver transplantation is an effective treatment for children with urea cycle disorders, correcting enzymatic defects and preventing neurologic injury. Factors such as increasing weight, male sex, and specific UCD diagnoses are associated with reduced risk of graft loss, while longer waitlist time and being male increase the odds of long-term cognitive delay. Early evaluation for LT in children with UCDs is recommended to optimize cognitive outcomes and prevent progressive neurologic injury.
LIVER TRANSPLANTATION
(2021)
Article
Gastroenterology & Hepatology
Koji Imoto, Masatake Tanaka, Takeshi Goya, Tomomi Aoyagi, Motoi Takahashi, Miho Kurokawa, Shigeki Tashiro, Masaki Kato, Motoyuki Kohjima, Yoshihiro Ogawa
Summary: This study investigated the mechanism of hyperammonemia induced by corticosteroid administration in a mouse model of OTCD. The results showed that corticosteroids induced hyperammonemia in OTCD mice by both muscle catabolism and suppression of gene expressions related to the urea cycle. Early intervention with renal replacement therapy should be considered in corticosteroid-induced UCD patients to prevent brain injuries or fatal outcomes.
BMC GASTROENTEROLOGY
(2022)
Article
Medical Laboratory Technology
MariaAnna Messina, Federica Raudino, Riccardo Iacobacci, Concetta Meli, Agata Fiumara
Summary: The study utilized tandem mass spectrometry to analyze the Gln/Glu ratio in blood specimens of patients with proximal urea cycle disorders (PUCDs) and found a significant elevation of the ratio in PUCD patients, suggesting it could be a useful diagnostic marker. Further analysis of blood spots from neonatal populations may lead to the inclusion of this ratio in newborn screening panels.
CLINICA CHIMICA ACTA
(2021)
Review
Biochemistry & Molecular Biology
Berna Seker Yilmaz, Paul Gissen
Summary: Ornithine transcarbamylase deficiency (OTCD) is a common urea cycle disorder that requires improved treatment options. Liver transplantation is currently the only curative choice, but it is limited by donor shortage, immunosuppression risks, and technical challenges. Gene therapy, including AAV gene addition, mRNA therapy, and genome editing, has shown promise as an alternative treatment approach. This review summarizes the current progress and challenges in clinical translation, discusses ongoing clinical trials, and outlines future directions for gene therapy development in OTCD.
Article
Medicine, General & Internal
Rastislav Sysak, Katarina Brennerova, Romana Krlin, Peter Stencl, Igor Rusnak, Maria Vargova
Summary: Ornithine transcarbamylase deficiency can lead to hyperammonemia in pregnant women, particularly in the first week after delivery. This article emphasizes the importance of strict adherence to protein intake recommendations and multidisciplinary monitoring for pregnant patients with OTC deficiency. It also discusses a case of severe hepatic failure in an OTC deficient patient during pregnancy.
Article
Neurosciences
Bjarke Hammer Niclasen, Maria Therese Schelde-Olesen, Mads Astvad, Anders Lokke, Thomas Kroigard, Helle H. Nielsen
Summary: Hyperammonaemic encephalopathy in adults is a rare condition that is often caused by a metabolic error in the urea cycle, but can also be triggered by exogenous factors. Swift diagnosis and treatment are crucial, and awareness of the condition and its possible causes can improve prognosis.
Article
Genetics & Heredity
Kathryn Clarkston, Joy Lee, Sarah Donoghue, Heidi Peters, Hernan Eiroa, Amit A. Shah, Kathleen Loomes, Jessica Wen, Mark Oliver, Winita Hardikar, Carlos E. Prada, Akihiro Asai
Summary: This study describes 10 females with ornithine transcarbamylase (OTC) deficiency and liver dysfunction, showing a unique pattern of hepatocyte injury where initial hyperammonemia and coagulopathy is followed by a delayed peak in aminotransferase levels. Five patients eventually underwent liver transplant for recurrent metabolic crises. Further investigations into the pathophysiology of liver dysfunction in OTC-deficient patients are needed to develop therapies and prevent the need for liver transplant.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Clinical Neurology
Svenja Scharre, Roland Posset, Sven F. Garbade, Florian Gleich, Marie J. Seidl, Ann-Catrin Druck, Juergen G. Okun, Andrea L. Gropman, Sandesh C. S. Nagamani, Georg F. Hoffmann, Stefan Koelker, Matthias Zielonka
Summary: This study developed a severity-adjusted classification system based on residual enzymatic OTC activity for predicting disease severity in male individuals with OTC-D. Residual enzymatic OTC activity was found to reliably predict disease severity and could serve as a tool for adjusting therapeutic strategies.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Review
Genetics & Heredity
Jun Kido, Keishin Sugawara, Takaaki Sawada, Shirou Matsumoto, Kimitoshi Nakamura
Summary: There is a relationship between the onset time, severity, and genetic mutation in male OTCD patients, with the level of OTC deactivation dependent on pathogenic variants.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Katarzyna Kowalczyk, Magdalena Bartnik-Glaska, Marta Smyk, Izabela Plaskota, Joanna Bernaciak, Marta Kedzior, Barbara Wisniowiecka-Kowalnik, Marta Deperas, Justyna Domaradzka, Alicja Luszczek, Daria Dutkiewicz, Agata Kozar, Dominika Grad, Magdalena Niemiec, Kamila Ziemkiewicz, Roza Magdziak, Natalia Braun-Walicka, Artur Barczyk, Maciej Geremek, Jennifer Castaneda, Anna Kutkowska-Kazmierczak, Pawel Wlasienko, Krystyna Jakubow-Durska, Marzena Debska, Anna Kucinska-Chahwan, Szymon Kozlowski, Boyana Mikulska, Tadeusz Issat, Tomasz Roszkowski, Agnieszka Nawara-Baran, Agata Runge, Anna Jakubiuk-Tomaszuk, Anna Kruczek, Ewa Kostyk, Grzegorz Pietras, Janusz Limon, Jerzy Zwolinski, Karolina Ochman, Tomasz Szajner, Piotr Wegrzyn, Miroslaw Wielgos, Maria Sasiadek, Ewa Obersztyn, Beata Anna Nowakowska
Summary: The aim of this study was to determine the suitability of the aCGH technique for prenatal diagnosis and assess the frequency of chromosomal aberrations not included in the diagnostic report. The study included 7400 prenatal cases and found a 27.2% chromosomal aberration detection rate, with 71.2% being numerical aberrations and 28.8% being structural aberrations. Clinically significant CNVs were detected in 6.8% of cases, and variants of unknown clinical significance were found in 0.7% of cases. The detection rate of clinically significant submicroscopic CNVs varied among different indications for invasive testing.
Article
Immunology
Danielle Rodrigues Cortez, Fabio Mitsuo Lima, Joao Luis Reis-Cunha, Daniella Castanheira Bartholomeu, Rolando Andre Rios Villacis, Silvia Regina Rogatto, Andre Guilherme Costa-Martins, Fernanda Sycko Marchiano, Rafaela Andrade do Carmo, Jose Franco da Silveira, Marjorie Mendes Marini
Summary: In this study, the genetic differences between two lineages of Chagas disease-causing parasite T. cruzi were analyzed using intraspecific array-based comparative genomic hybridization (aCGH). The results showed that clone D11 had more chromosomal gains and losses compared to the parental G strain. These genomic changes suggest a dynamic genome in clone D11 that responds to environmental stress by altering gene copy numbers and generating segmental aneuploidy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Neurosciences
Piotr Niwinski, Barbara Remberk, Filip Rybakowski, Dariusz Rokicki
Summary: The paper discusses the challenges of diagnosing a somatic condition alongside psychiatric symptoms, using a case study of a 15-year-old girl eventually diagnosed with ornithine transcarbamylase (OTC) deficiency. It highlights that OTC deficiency in females is less fully expressed and can go undiagnosed for years due to X chromosome inactivation, presenting with symptoms such as nausea, migraines, and dietary protein avoidance. The study concludes that somatic comorbidity in psychiatric inpatients is common but often overlooked in diagnosis and treatment.
NEUROPSYCHOBIOLOGY
(2021)