Article
Biochemistry & Molecular Biology
Andrea Bazo, Aquilino Lantero, Itsaso Mauleon, Leire Neri, Martin Poms, Johannes Haberle, Ana Ricobaraza, Bernard Benichou, Jean-Philippe Combal, Gloria Gonzalez-Aseguinolaza, Rafael Aldabe
Summary: This study evaluated the therapeutic efficacy of gene therapy for treating Citrullinemia type I (CTLN1). The results showed that this treatment method can improve the condition and increase the survival rate of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Melissa Daou, Mirna Souaid, Tony Yammine, Issam Khneisser, Hicham Mansour, Nabiha Salem, Antony Nemr, Johnny Awwad, Adib Moukarzel, Chantal Farra
Summary: This study investigated citrullinemia type 1 (CTLN1) in the Middle East and found a total of seven variants. Two novel variants were associated with early-onset and severe clinical presentation, while five known variants were associated with diverse clinical presentations.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Cell Biology
Yu Fujita, Tokio Hoshina, Juntaro Matsuzaki, Yusuke Yoshioka, Tsukasa Kadota, Yusuke Hosaka, Shota Fujimoto, Hironori Kawamoto, Naoaki Watanabe, Kenji Sawaki, Yohei Sakamoto, Makiko Miyajima, Kwangyole Lee, Kazuhiko Nakaharai, Tetsuya Horino, Ryo Nakagawa, Jun Araya, Mitsuru Miyato, Masaki Yoshida, Kazuyoshi Kuwano, Takahiro Ochiya
Summary: The study identified EV COPB2 protein as a potential early predictive biomarker for severity of COVID-19, showing excellent predictive value in both discovery and validation cohorts.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Multidisciplinary Sciences
Andres Roncancio-Clavijo, Miriam Gorostidi-Aicua, Ainhoa Alberro, Andrea Iribarren-Lopez, Ray Butler, Raul Lopez, Jose Antonio Iribarren, Diego Clemente, Jose Maria Marimon, Javier Basterrechea, Bruno Martinez, Alvaro Prada, David Otaegui
Summary: The COVID-19 pandemic has challenged the protocols and capacity of hospitals, especially in managing severe patients in Intensive Care Units. Various models have been proposed to predict mortality and severity, but there is no clear consensus on their use. This study utilized data from routine blood tests performed on the first day of hospitalization to generate a predictive model using artificial intelligence, which can identify the risk of developing severe disease. The findings underscore the importance of studying routine analytical variables early in hospital admission and the benefits of applying AI to identify high-risk patients.
Article
Clinical Neurology
Dibashree Tamuli, Manpreet Kaur, Ashok K. Jaryal, Achal K. Srivastava, Kishore K. Deepak
Summary: This study aimed to evaluate the integrity of the autonomic nervous system in patients with spino-cerebellar ataxia (SCA) type 1 and 2 by conducting autonomic function tests and scoring with composite autonomic severity score (CASS). The results showed a reduction in cardiovascular autonomic reactivity parameters, particularly a significant decrease in systolic blood pressure and lower 30:15 ratio during head up tilt in both SCA1 and SCA2 patients compared to controls. Sudomotor assessment also revealed prolonged distal leg latency of sweat response in SCA1 patients. The use of CASS indicated the presence of moderate autonomic failure in the majority of SCA1 and SCA2 patients.
JOURNAL OF CLINICAL NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Yuheng Yuan, Bianca Dimitrov, Nikolas Boy, Florian Gleich, Matthias Zielonka, Stefan Koelker
Summary: In this study, we investigated the relationship between genotype and phenotype in individuals with glutaric aciduria type 1 (GA1). We found that mutations in the glutaryl-CoA dehydrogenase (GCDH) gene led to decreased enzyme activity and increased levels of glutaric acid and 3-hydroxyglutaric acid in urine. Additionally, we discovered that higher protein expression of GCDH was associated with acute encephalopathic crisis and increased in silico protein stability.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Immunology
Minyue Yin, Rufa Zhang, Zhirun Zhou, Lu Liu, Jingwen Gao, Wei Xu, Chenyan Yu, Jiaxi Lin, Xiaolin Liu, Chunfang Xu, Jinzhou Zhu
Summary: This study explored different machine learning models for early identification of severe acute pancreatitis among patients with acute pancreatitis and found that the AutoML model based on the GBM algorithm showed the best performance, demonstrating its clinical practicability.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Yuan Liu, Yi Luo, Lei Xia, Bijun Qiu, Tao Zhou, Mingxuan Feng, Chenchen Wang, Feng Xue, Xiaosong Chen, Longzhi Han, Jianjun Zhang, Qiang Xia
Summary: This study evaluated the outcomes of liver transplantation in neonatal-onset citrullinemia type I patients, showing that transplantation can restore metabolic function, improve developmental delay, and neurological deficits. For patients with severe hyperammonemia insults, liver transplantation should be conducted at an early age to prevent further neurological or developmental deficits.
Article
Medicine, General & Internal
Attila Rutai, Bettina Zsikai, Szabolcs Peter Tallosy, Daniel Erces, Lajos Bizanc, Laszlo Juhasz, Marietta Zita Poles, Jozsef Soki, Zain Baaity, Roland Fejes, Gabriella Varga, Imre Foldesi, Katalin Burian, Andrea Szabo, Mihaly Boros, Jozsef Kaszaki
Summary: The study aims to develop a standardized research protocol to reproducibly characterize the progression of sepsis-related events within clinically-relevant time frames.
FRONTIERS IN MEDICINE
(2022)
Article
Physiology
Heewon Chung, Chul Park, Wu Seong Kang, Jinseok Lee
Summary: This study investigates the model bias that arises when training AI models using datasets from only one gender in medical domains. The findings show that training an AI model with gender-specific data can lead to decreased accuracy when applied to testing data of the opposite gender, highlighting the importance of mitigating gender bias in AI models for accurate predictions in healthcare applications.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Larissa Delmonego, Thayna Patachini Maia, Debora Delwing-Dal Magro, Karine Louize Vincenzi, Aline Barbosa Lima, Luana Carla Pscheidt, Leticia Eger, Daniela Delwing-de Lima
Summary: Citrullinemia and ammonia induce oxidative stress in the cerebrum of rats, while resveratrol exerts antioxidant effects against these substances.
METABOLIC BRAIN DISEASE
(2021)
Article
Food Science & Technology
Zhaodi Zhang, Jiahong Li, Ming Zhang, Binbin Li, XiaoHua Pan, Xiaoliang Dong, Li-Long Pan, Jia Sun
Summary: The role of GPR109a receptor in type 1 diabetes (T1D) and its underlying mechanisms were investigated in this study. It was found that GPR109a deficiency accelerated the development of T1D and activated the M1 macrophage polarization, disrupting the pancreatic immune homeostasis. Activation of GPR109a on macrophages by dietary components may provide a new strategy for preventing or treating T1D.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Endocrinology & Metabolism
Natsuko Arai-Ichinoi, Atsuo Kikuchi, Yoichi Wada, Osamu Sakamoto, Shigeo Kure
Summary: Citrin deficiency can manifest at different symptomatic periods from neonatal period to adulthood with diverse clinical presentations. Diagnosis is crucial before the development of severe manifestations but can be challenging, as not all patients are detected through newborn mass screening and undiagnosed patients may appear healthy in childhood. Recognizing characteristics such as food preferences and history of infantile hepatopathy may aid in diagnosing citrin deficiency in childhood, particularly in cases of severe hypoglycemia or growth failure.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Endocrinology & Metabolism
Leena Mamilly, Lucy D. Mastrandrea, Claudia Mosquera Vasquez, Brett Klamer, Mahmoud Kallash, Ahmad Aldughiem
Summary: Diabetic nephropathy is a common microvascular complication in type 1 diabetes mellitus. Urinary markers of renal damage or oxidative stress may signal early stages of DN, but their association with blood pressure patterns and glycemic variability in children is not yet well understood. This study found that while microalbuminuria was negative, urinary NGAL/Cr and pentosidine/Cr ratios were significantly elevated in diabetic patients. Additionally, poor nocturnal systolic blood pressure dipping was found in nearly half of the cases, and urinary NGAL/Cr negatively correlated with this dipping pattern. Both NGAL/Cr and pentosidine/Cr ratios were also higher in the high glycemic variability group. Overall, this pilot study highlights the potential role of ABPM and urinary markers in the early detection of diabetic nephropathy, with glycemic variability possibly playing a role in the disease process.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Pediatrics
Mei Xiong, Mingwu Chen
Summary: This study identified two novel mutations that cause citrullinemia type I and found that the blood ammonia level of the neonatal form of citrullinemia was markedly higher than other types. The genotype-phenotype association in Chinese patients remains unclear and should be further evaluated in genetic studies with larger sample sizes.
FRONTIERS IN PEDIATRICS
(2022)
Article
Endocrinology & Metabolism
Ulrike Mutze, Sven F. Garbade, Florian Gleich, Martin Lindner, Peter Freisinger, Julia B. Hennermann, Eva Thimm, Gwendolyn Gramer, Roland Posset, Johannes Kraemer, Sarah C. Gruenert, Georg F. Hoffmann, Stefan Koelker
Summary: Newborn screening for inherited metabolic diseases can lead to early treatment and better clinical outcomes. This study evaluated the growth of individuals with IMDs under different dietary regimes. The results showed that there were variations in growth and body measurements among the screened individuals, with diet playing a significant role in linear growth.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Endocrinology & Metabolism
Ulrike Muetze, Florian Gleich, Ivo Baric, Mathias Baumgartner, Alberto Burlina, Kimberly A. Chapman, Yin-Hsiu Chien, Elisenda Cortes-Saladelafont, Corinne De Laet, Dries Dobbelaere, Francois Eysken, Matthias Gautschi, Rene Santer, Johannes Haeberle, Clara Joaquin, Daniela Karall, Martin Lindner, Allan M. Lund, Chris Muehlhausen, Elaine Murphy, Dominique Roland, Angeles Ruiz Gomez, Anastasia Skouma, Sarah C. Gruenert, Margreet Wagenmakers, Sven F. Garbade, Stefan Koelker, Nikolas Boy
Summary: This study evaluates the impact of SARS-CoV-2 infections on medical health care and disease outcome in patients with intoxication-type inherited metabolic disorders. The findings indicate that most infected individuals experienced mild symptoms and did not require hospitalization, and no complications specific to inherited metabolic disorders or COVID-19 were observed.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Endocrinology & Metabolism
Patrick Forny, Friederike Hoerster, Matthias R. R. Baumgartner, Stefan Koelker, Nikolas Boy
Summary: Organic acidurias, such as GA1, MMA, and PA, have guidelines for diagnosis and management, but the development of these guidelines is hindered by limited evidence. Observational studies have contributed to improving the quality of evidence and guiding the formulation of guideline recommendations, but there are still significant gaps in evidence regarding prognosis and treatment.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Pediatrics
Alexander Kovacevic, Sven F. Garbade, Friederike Hoerster, Georg F. Hoffmann, Matthias Gorenflo, Derliz Mereles, Stefan Koelker, Christian Staufner
Summary: This study finds that right ventricular dysfunction is common in propionic acidemia patients, with diastolic dysfunction being particularly prevalent. These functional abnormalities are closely associated with the clinical outcome of the patients.
Article
Pediatrics
Thilde Nordmann Winther, Alex Yde Nielsen, Allan Lund, Fin Stolze Larsen, Marianne Horby Jorgensen
Summary: This study retrospectively evaluated a systematic diagnostic approach to paediatric acute liver failure (P-ALF) in Denmark and collected nationwide epidemiological data. The results showed that identifying the aetiology in 82% of cases led to improved outcomes for P-ALF. Therefore, establishing the cause is of great significance for treatment and prognosis.
Article
Genetics & Heredity
Emilie Erbs, Claus Lohman Brasen, Allan Meldgaard Lund, Maria Rasmussen
Summary: This study reports a case of a 30-year-old male patient with NADSYN1 associated congenital NAD deficiency disorder, presenting various skeletal malformations and facial feature abnormalities. Through genetic sequencing and analysis of NAD levels, a homozygous missense variant in the NADSYN1 gene was identified in the patient, with decreased NAD levels. Supplementation with nicotinamide resulted in an increase in NAD levels.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Pediatrics
Swathi Sunil Rao, Gandham Srilakshmi Bhavani, Anil B. B. Jalan, Rathika D. D. Shenoy
Summary: Progressive encephalopathy with brain edema and/or leukoencephalopathy type 1 (PEBEL1) is a rare mitochondrial disorder caused by NAXE gene variation, leading to impaired repair mechanism. Patients usually experience rapid neurological deterioration and death after high-grade fever in infancy. Limited cases have been reported and survival rate is low. This study presents two surviving infants with PEBEL1 from unrelated Indian families and contributes to the understanding of this disease.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Endocrinology & Metabolism
Yuheng Yuan, Bianca Dimitrov, Nikolas Boy, Florian Gleich, Matthias Zielonka, Stefan Koelker
Summary: In this study, we investigated the relationship between genotype and phenotype in individuals with glutaric aciduria type 1 (GA1). We found that mutations in the glutaryl-CoA dehydrogenase (GCDH) gene led to decreased enzyme activity and increased levels of glutaric acid and 3-hydroxyglutaric acid in urine. Additionally, we discovered that higher protein expression of GCDH was associated with acute encephalopathic crisis and increased in silico protein stability.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Editorial Material
Endocrinology & Metabolism
Shamima Rahman, Marc Patterson, Verena Peters, Eva Morava, Johannes Zschocke, Matthias Baumgartner
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Elaine Zaunseder, Ulrike Muetze, Sven F. Garbade, Saskia Haupt, Patrik Feyh, Georg F. Hoffmann, Vincent Heuveline, Stefan Koelker
Summary: Isovaleric aciduria (IVA) is a rare disorder of leucine metabolism that is included in newborn screening programs worldwide. However, the effectiveness of IVA screening is hindered by the identification of individuals with a milder variant of the disease and an increasing number of false positive results. In this study, machine learning methods were used to improve the classification of IVA, resulting in a significant reduction in false positive rates while maintaining high sensitivity.
Article
Endocrinology & Metabolism
Ulrike Muetze, Lucy Henze, Julian Schroeter, Florian Gleich, Martin Lindner, Sarah C. Gruenert, Ute Spiekerkoetter, Rene Santer, Eva Thimm, Regina Ensenauer, Johannes Weigel, Skadi Beblo, Maria Arelin, Julia B. Hennermann, Iris Marquardt, Peter Freisinger, Johannes Kraemer, Andrea Dieckmann, Natalie Weinhold, Katharina A. Schiergens, Esther M. Maier, Georg F. Hoffmann, Sven F. Garbade, Stefan Koelker
Summary: Newborn screening is useful in identifying individuals with rare diseases like isovaleric aciduria. In this study, metabolic decompensation in isovaleric aciduria was associated with higher levels of isovalerylcarnitine (C5) and urinary isovalerylglycine. The first screening sample and confirmatory testing can be reliable early predictors of the disease's clinical course.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Nutrition & Dietetics
Elena Schnabel, Stefan Koelker, Florian Gleich, Patrik Feyh, Friederike Hoerster, Dorothea Haas, Junmin Fang-Hoffmann, Marina Morath, Gwendolyn Gramer, Wulf Roeschinger, Sven F. Garbade, Georg F. Hoffmann, Juergen G. Okun, Ulrike Muetze
Summary: Newborn screening programs are effective measures of secondary prevention and have been extended. This study evaluated the screening for several disorders and identified disease variants that can be treated with cofactors.
Article
Medicine, Research & Experimental
Jordan Kho, Urszula Polak, Ming-Ming Jiang, John D. Odom, Jill V. Hunter, Saima M. Ali, Lindsay C. Burrage, Sandesh C. S. Nagamani, Robia G. Pautler, Hannah P. Thompson, Akihiko Urayama, Zixue Jin, Brendan Lee
Summary: Nitric oxide (NO) is a critical signaling molecule implicated in neurocognitive diseases. Excessive and insufficient NO production have both been linked to pathology. This study investigates the effects of NO on brain endothelial cells and the blood-brain barrier using a model of NO deficiency. The results suggest that ASL-mediated NO synthesis is necessary for maintaining brain microvascular endothelial cell functions and BBB integrity.