Article
Oncology
Abderrahim Oussalah, Youssef Siblini, Sebastien Hergalant, Celine Chery, Pierre Rouyer, Catia Cavicchi, Renzo Guerrini, Pierre-Emmanuel Morange, David Tregouet, Mihaela Pupavac, David Watkins, Tomi Pastinen, Wendy K. Chung, Can Ficicioglu, Francois Feillet, D. Sean Froese, Matthias R. Baumgartner, Jean-Francois Benoist, Jacek Majewski, Amelia Morrone, David S. Rosenblatt, Jean-Louis Gueant
Summary: This study found that splicing mutations in the antisense PRDX1 gene led to epigenetic silencing of MMACHC and TESK2 in epi-cblC patients, termed as "epi-digenism". This phenomenon is not common in cblC patients, suggesting further research on the potential impact on cancer risk and spermatogenesis.
CLINICAL EPIGENETICS
(2022)
Article
Pediatrics
Ambika Gupta, Madhulika Kabra, Neerja Gupta
Summary: MAHCC, a rare genetic disorder, can lead to cardiovascular complications, especially in children presenting with unexplained pulmonary arterial hypertension. Elevated plasma homocysteine level may serve as a simple screening modality for this disorder. Accurate diagnosis is crucial for managing the condition effectively with hydroxocobalamin and betaine.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Article
Biochemistry & Molecular Biology
Rosa Passantino, Maria Rosalia Mangione, Maria Grazia Ortore, Maria Assunta Costa, Alessia Provenzano, Heinz Amenitsch, Raffaele Sabbatella, Caterina Alfano, Vincenzo Martorana, Silvia Vilasi
Summary: cblC disease is a congenital disorder characterized by metabolic dysfunction and severe clinical symptoms. A common mutation, p.R132X, was found to retain partial function and maintain structural stability. This study provides insights into the structural and functional properties of the mutant protein MMACHC-R132X and its binding affinity for Cbl.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2022)
Review
Genetics & Heredity
Silvia Kalantari, Brigida Brezzi, Valeria Bracciama, Antonella Barreca, Paolo Nozza, Tiziana Vaisitti, Antonio Amoroso, Silvia Deaglio, Marco Manganaro, Francesco Porta, Marco Spada
Summary: Adult onset CblC disease is a rare disorder with a variety of symptoms, including neurological, psychiatric, renal, ophthalmic and thromboembolic symptoms. Diagnosis can be delayed due to poor awareness of the disease among medical professionals. Treatment with hydroxycobalamin is effective in reversing symptoms. Adult patients usually have compound heterozygous variants in the MMACHC gene. It is important to consider CblC disease in the differential diagnosis of adult patients with specific symptoms.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Clinical Neurology
Li Zhou, Qin Yang
Summary: This case report highlights the importance of considering inborn errors of metabolism in teenagers presenting with challenging or neurologic symptoms, especially when combined with unexplained heart diseases.
Article
Biochemistry & Molecular Biology
Rajdeep Kaur, Savita Verma Attri, Arushi Gahlot Saini, Naveen Sankhyan
Summary: Cobalamin C defect is caused by pathogenic variants in the MMACHC gene, resulting in the accumulation of methylmalonic acid and homocysteine. Neurological manifestations are the most common symptoms in affected individuals, indicating a potential target for read-through therapeutics.
Article
Cell Biology
Arnaud Wedemann, Abderrahim Oussalah, Nathalie Lamireau, Maurane Theron, Melissa Julien, Jean-Philippe Mergnac, Baptiste Augay, Pauline Deniaud, Tom Alix, Marine Frayssinoux, Francois Fellet, Jean-Louis Gueant
Summary: Inherited disorders of vitamin B-12 metabolism can cause various manifestations, potentially influenced by age and related genes. The cytoplasmic transport cluster is associated with neurological and ophthalmological manifestations, the mitochondrion cluster with hypotonia, acute metabolic decompensation, and death, and the B-12 availability and remethylation clusters with anemia and cytopenia. Younger patients primarily show symptoms like hypotonia, while older patients predominantly exhibit neurological symptoms and thromboembolic manifestations.
CELL REPORTS MEDICINE
(2022)
Article
Medicine, General & Internal
Qiang Wang, Qi Wang, Yanxia Gao, Chenquan Tang, Zhaoli Gao, Zhao Hu
Summary: Membranous nephropathy secondary to cobalamin C disease can be reversed with timely intervention, as demonstrated in this case report.
FRONTIERS IN MEDICINE
(2022)
Article
Clinical Neurology
Shengnan Wang, Xu Wang, Jianxin Xi, Wenzhuo Yang, Mingqin Zhu
Summary: This study reports a case of a 29-year-old female patient who presented with symptoms of encephalitis and was diagnosed with Methylmalonic acidemia. Genetic analysis revealed a novel homozygous mutation in the MMACHC gene. The patient showed significant improvement with intramuscular adenosine cobalamin treatment. The findings suggest that metabolic diseases should be considered in patients with symmetrical brain lesions.
FRONTIERS IN NEUROLOGY
(2022)
Article
Genetics & Heredity
Si Ding, Shiying Ling, Lili Liang, Wenjuan Qiu, Huiwen Zhang, Ting Chen, Xia Zhan, Feng Xu, Xuefan Gu, Lianshu Han
Summary: Late-onset cblC defect is a common type of methylmalonic acidemia in China. This study analyzed the clinical characteristics and long-term outcomes of Chinese patients with late-onset cblC defect. The study found that the age of onset ranged from 2 to 32.8 years old. Neuropsychiatric symptoms were the most common initial symptoms, and cognitive decline became the most frequent symptom overall. Treatment resulted in significant decrease in metabolite levels. Mutations in the MMACHC gene were identified, with the c.482G>A variant being the most frequent. Delayed diagnosis was found to be an independent risk factor for poor outcomes.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Clinical Neurology
Anthony M. Gacita, Alma Bicknese, Katherine Kim, Frank Zelko, Joshua Baker
Summary: Cobalamin-G deficiency is a rare inborn error of metabolism that affects the utilization of vitamin B12, leading to various neurological symptoms. This case report describes an 18-year-old woman with progressive dementia and encephalopathy, whose diagnosis of cobalamin-G deficiency was confirmed by genetic and biochemical testing. Treatment with leucovorin, betaine, and B12 injections resulted in a gradual improvement in cognitive function. This report highlights the importance of considering cobalamin-G deficiency in cases of dementia in young adults.
Article
Oncology
Catia Cavicchi, Abderrahim Oussalah, Silvia Falliano, Lorenzo Ferri, Alessia Gozzini, Serena Gasperini, Serena Motta, Miriam Rigoldi, Giancarlo Parenti, Albina Tummolo, Concetta Meli, Francesca Menni, Francesca Furlan, Marta Daniotti, Sabrina Malvagia, Giancarlo la Marca, Celine Chery, Pierre-Emmanuel Morange, David Tregouet, Maria Alice Donati, Renzo Guerrini, Jean-Louis Gueant, Amelia Morrone
Summary: The study found that all 11 cblC patients actually had epi-cblC disease, with one patient having a bi-allelic MMACHC epimutation. It is concluded that epi-cblC is an underestimated cause of inborn errors of cobalamin metabolism, and the clinical phenotype of epi-cblC patients is similar to that of canonical cblC patients.
CLINICAL EPIGENETICS
(2021)
Article
Psychiatry
Monika Chhajed, Pradeep Kumar Gunasekaran, Lokesh Saini, Indar Kumar Sharawat
Summary: A 9-year-old boy presented with a 6-month history of abnormal behavior, including unprovoked aggression and occasional self-inflicting behavior. He also exhibited decreased appetite, anhedonia, apathy, reduced sleep, low energy, and poor interaction with parents and peers. Assessment revealed mild cognitive impairment, below-average intelligence, moderate depression, mild psychotic symptoms, macrocytic anemia, and low vitamin B12 levels. Next-generation sequencing identified a novel mutation in the MMACHC gene, suggesting combined methylmalonic aciduria and homocystinuria (cblC type). Timely initiation of therapy can improve long-term neurological outcomes.
ASIAN JOURNAL OF PSYCHIATRY
(2022)
Article
Genetics & Heredity
Zhehui Chen, Hui Dong, Yupeng Liu, Ruxuan He, Jinqing Song, Ying Jin, Mengqiu Li, Yi Liu, Xueqin Liu, Hui Yan, Jianguang Qi, Fang Wang, Huijie Xiao, Hong Zheng, Lulu Kang, Dongxiao Li, Yao Zhang, Yanling Yang
Summary: Late-onset cblC deficiency patients exhibit a wide range of neuropsychiatric symptoms and other presentations, including multiple organ damage, which can easily be misdiagnosed. Metabolic and genetic studies are crucial for accurate diagnosis, and metabolic treatment appears to be beneficial.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Obstetrics & Gynecology
Shuang Hu, Xiangdong Kong
Summary: This study investigated the phenotypes, biochemical features, and genotypes of 244 pedigrees with methylmalonic aciduria (MMA) in China. Genetic analysis was found to be a convenient method for prenatal diagnosis, aiding in the prevention of MMA patients being born.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Camila M. Otero, Guillermina Boggan Simal, Magali F. Scocozza, Aldo Rubert, Claudia A. Grillo, Luciana Hannibal, Gabriel Lavorato, Maria Ana Huergo, Daniel H. Murgida, Carolina Vericat
Summary: This study presents a post-synthesis optimization and characterization method for biocompatible gold nanotriangles (Au NTs), which can be efficiently separated from spherical gold nanoparticles using depletion forces. The study also analyzes the cytotoxic effects of surface sulfide species and residual presence of surfactant and demonstrates the successful application of Au NTs in photothermal conversion.
ACS APPLIED NANO MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Aida Corrillero Bravo, Maria Nieves Ligero Aguilera, Nahuel R. Marziali, Lennart Moritz, Victoria Wingert, Katharina Klotz, Anke Schumann, Sarah C. Gruenert, Ute Spiekerkoetter, Urs Berger, Ann-Kathrin Lederer, Roman Huber, Luciana Hannibal
Summary: S-adenosylmethionine (SAM) is essential for methyl transfer reactions. SAM is produced de novo via the methionine cycle. The demethylation of SAM produces S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases. Measurement of SAM and SAH in plasma is valuable for diagnosing inborn errors of metabolism and assessing methyl group homeostasis.
Article
Genetics & Heredity
Vanessa Huebner, Luciana Hannibal, Nils Janzen, Sarah Catharina Gruenert, Peter Freisinger
Summary: Methionine adenosyltransferase I/III deficiency, caused by mutations in the MAT1A gene, can lead to hypermethioninemia in newborns. This study reports on a female patient with elevated methionine concentrations in newborn screening. With dietary management, her neurological development was age-appropriate.
Article
Multidisciplinary Sciences
Rens Peeters, Jorge Cuenca-Escalona, Esther A. Zaal, Anna T. Hoekstra, Anouk C. G. Balvert, Marcos Vidal-Manrique, Niek Blomberg, Sjoerd J. van Deventer, Rinke Stienstra, Julia Jellusova, Martin Giera, Luciana Hannibal, Ute Spiekerkoetter, Martin Ter Beest, Celia R. Berkers, Annemiek B. van Spriel
Summary: This study identifies CD37 as a crucial membrane protein that inhibits fatty acid metabolism in aggressive B-cell lymphoma. Deletion of CD37 leads to increased fatty acid oxidation and depletion of palmitate from serum. CD37 interacts with the fatty acid transporter FATP1 to inhibit the uptake of palmitate. Inhibition of CD37 results in the uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation. Patients with CD37-negative lymphomas exhibit large lipid deposits and intracellular lipid droplets. Inhibition of carnitine palmitoyl transferase 1 A compromises viability and proliferation of CD37-deficient lymphomas.
NATURE COMMUNICATIONS
(2022)
Article
Environmental Sciences
Ann-Kathrin Lederer, Maximilian Andreas Storz, Roman Huber, Luciana Hannibal, Elena Neumann
Summary: Short-term intervention with a vegan diet can improve concentrations of adiponectin and leptin, but the effects may vary depending on sex.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Editorial Material
Nutrition & Dietetics
Ali Niklewicz, A. David Smith, Alison Smith, Andre Holzer, Andrew Klein, Andrew McCaddon, Anne M. Molloy, Bruce H. R. Wolffenbuttel, Ebba Nexo, Helene McNulty, Helga Refsum, Jean-Louis Gueant, Marie-Joe Dib, Mary Ward, Michelle Murphy, Ralph Green, Kourosh R. Ahmadi, Luciana Hannibal, Martin J. Warren, P. Julian Owen
Summary: Vitamin B-12 deficiency is common among vegetarians and vegans, especially pregnant women or women of child-bearing age. It is associated with increased risk of neuro, vascular, immune, and inflammatory disorders. However, the current recommended nutrient intake for vitamin B-12 does not adequately consider the needs of individuals choosing a plant-based diet.
EUROPEAN JOURNAL OF NUTRITION
(2023)
Article
Endocrinology & Metabolism
Lennart Moritz, Katharina Klotz, Sarah Catharina Gruenert, Luciana Hannibal, Ute Spiekerkoetter
Summary: Phenylketonuria (PKU) is a common inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). PKU patients have elevated levels of phenylalanine and may experience intellectual disability. This study found distinct differences in metabolite profiles between PKU patients and healthy controls, as well as altered concentrations of metabolites in treated patients. The PKU submetabolome identified in this study reflects the effects of dietary adherence, compensatory metabolic pathways, and metabolic disturbances that cannot be corrected with diet. Potential therapeutic targets may be discovered to approximate the submetabolome of PKU patients to that of healthy controls and prevent long-term organ damage.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Multidisciplinary Sciences
Anke Schumann, Marion Brutsche, Monique Havermans, Sarah C. Gruenert, Stefan Koelker, Olaf Gross, Luciana Hannibal, Ute Spiekerkoetter
Summary: Methylmalonic aciduria (MMA-uria) is a condition caused by a lack of the enzyme methylmalonyl-CoA mutase (MUT) in mitochondria. It affects energy generation from certain amino acids, fatty acids, and cholesterol. Chronic kidney disease (CKD) is a known complication of MMA-uria. Research has shown that MMA-uria cells have increased creatinine levels and decreased antioxidant defense. Mitochondrial homeostasis is disrupted, with changes in metabolites and impaired energy generation from fatty acid oxidation. Potentially toxic metabolite methylcitrate is increased under high protein and isoleucine/valine conditions. Mitophagy is disabled, while autophagy is active, especially under high protein and isoleucine/valine conditions. Mitochondrial dynamics shift towards fission and the stress-resistance protein Sirtuin1 is down-regulated. Overall, these findings highlight the role of protein toxicity and provide insight into how accumulating toxic organic acids may contribute to CKD in MMA-uria.
SCIENTIFIC REPORTS
(2023)
Article
Psychiatry
Kimon Runge, Marco Reisert, Bernd Feige, Kathrin Nickel, Horst Urbach, Nils Venhoff, Andreas Tzschach, Miriam A. A. Schiele, Luciana Hannibal, Harald Pruess, Katharina Domschke, Ludger Tebartz van Elst, Dominique Endres
Summary: This study aimed to determine whether a comprehensive screening approach such as the Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD) is effective in detecting organic OCD forms. Results showed that out of the 61 patients analyzed, 5 were suspected to have organic OCD, including 3 with autoimmune OCD and 2 with newly diagnosed genetic syndromes. The study also revealed the presence of immunological abnormalities, particularly decreased neurovitamin levels and increased streptococcal and antinuclear antibodies, in the entire patient group.
TRANSLATIONAL PSYCHIATRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Joerg Buescher, Luciana Hannibal
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Medicine, General & Internal
Maximilian Andreas Storz, Alexander Mueller, Lisa Niederreiter, Amy M. Zimmermann-Klemd, Martin Suarez-Alvarez, Stefanie Kowarschik, Monique Strittmatter, Evelyn Schlachter, Cristian Pasluosta, Roman Huber, Luciana Hannibal
Summary: The study found that even among homogeneously healthy individuals, different diets led to measurable differences in dietary intake and health biomarkers. Plant-based diets, especially the vegan diet, showed the most favorable patterns of lipid metabolism and glycemic control, but had the lowest food intake of vitamin B12.
ANNALS OF MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Frances Winkler, Anna Hipp, Carlos Ramirez, Bianca Martin, Matteo Villa, Emilia Neuwirt, Oliver Gorka, Jeroen Aerssens, Susanne E. Johansson, Nisha Rana, Sian Llewellyn-Lacey, David A. Price, Marcus Panning, Olaf Gross, Erika L. Pearce, Carl M. Hermann, Kathrin Schumann, Luciana Hannibal, Christoph Neumann-Haefelin, Tobias Boettler, Percy Knolle, Maike Hofmann, Dirk Wohlleber, Robert Thimme, Bertram Bengsch
Summary: Exhausted T cells with limited function are common in chronic HBV and HCV infection, but the relationship between metabolism and exhaustion states, the impact of antiviral therapy, and the role of metabolic checkpoints in dysfunction are not fully understood.
Article
Nutrition & Dietetics
Julian Herter, Ann-Kathrin Lederer, Alvaro Luis Ronco, Luciana Hannibal, Roman Huber, Maximilian Andreas Storz
Summary: Chronic low-grade metabolic acidosis is a common occurrence in the Western world due to high intake of sulfur-containing amino acids from processed meats. This excess acid release leads to increased ammonia production by the kidneys, resulting in the breakdown of muscle tissue. A secondary data analysis from a dietary intervention study suggests that high dietary acid load is associated with higher serum concentrations of lysine and 1-methyl-histidine, while glutamine and glycine levels are reduced.
Article
Multidisciplinary Sciences
Fatemeh Mirzadeh Azad, Eduard A. Struys, Victoria Wingert, Luciana Hannibal, Ken Mills, Joop H. Jansen, Daniel B. Longley, Hendrik G. Stunnenberg, Yaser Atlasi
Summary: Understanding the mechanisms of epigenetic regulation in ESCs is crucial for stem cell and developmental biology. In this study, the identification of Spic as a marker of ground state pluripotency and its role in controlling 1C metabolism and histone marks highlight the importance of auxiliary TFs in linking cellular metabolism to epigenetic regulation in ESCs.
Review
Nutrition & Dietetics
Maximilian A. Storz, Alvaro L. Ronco, Luciana Hannibal
Summary: Contemporary Western diets are too acidic and lack potassium alkali salts, leading to low-grade metabolic acidosis. Plant-based diets, especially vegetarian and vegan diets, are most effective in reducing dietary acid load and offer measurable benefits for disease prevention and management.
JOURNAL OF NUTRITIONAL SCIENCE
(2022)