Review
Cell Biology
Ahmed Reda, Koenraad Veys, Martine Besouw
Summary: Cystinosis is a rare inheritable lysosomal storage disorder characterized by cystine accumulation, chronic kidney disease, and multiple extra-renal complications. Male patients are often infertile due to azoospermia, while female patients remain fertile. The fertility status of male patients has shifted from primary hypogonadism to azoospermia with cysteamine treatment.
Review
Cell Biology
Elizabeth G. Ames, Jess G. Thoene
Summary: Cystinosis is a lethal genetic disease with specific treatments. The cellular mechanisms are still unknown, but programmed cell death and apoptosis may be involved. Studies have shown that apoptosis rate is increased in cystinosis, but can be partially reversed with cysteamine.
Article
Plant Sciences
Maria Ermakova, Patricia E. Lopez-Calcagno, Robert T. Furbank, Christine A. Raines, Susanne von Caemmerer
Summary: Overexpression of SBPase does not improve photosynthesis in a model C-4 plant.
Article
Pharmacology & Pharmacy
Sabrina Klank, Christina van Stein, Marianne Grueneberg, Chris Ottolenghi, Kerstin K. Rauwolf, Juergen Grebe, Janine Reunert, Erik Harms, Thorsten Marquardt
Summary: Cystinosis is a severe inherited metabolic disorder caused by the buildup of cystine in the lysosomes. Lifelong treatment with cysteamine is necessary to break down the cystine. However, the current therapy has poor adherence due to frequent dosing and gastrointestinal side effects. This study compared two different formulations of cysteamine and found that delayed-release cysteamine had a more favorable pharmacokinetic profile and improved quality of life for patients. This alternative could also benefit those who do not have access to the approved delayed-release cysteamine.
Article
Cell Biology
Koenraad Veys, Sante Princiero Berlingerio, Dries David, Tjessa Bondue, Katharina Held, Ahmed Reda, Martijn van den Broek, Koen Theunis, Mirian Janssen, Elisabeth Cornelissen, Joris Vriens, Francesca Diomedi-Camassei, Rik Gijsbers, Lambertus van den Heuvel, Fanny O. Arcolino, Elena Levtchenko
Summary: In this study, kidney progenitor cells (KPCs) were found in the urine of cystinosis patients, which have the potential for regeneration and can differentiate into functional cells. Gene addition using lentiviral vector technology was effective in reducing cystine levels. This finding provides a novel tool for disease modeling.
Article
Biochemistry & Molecular Biology
Emirhan Nemutlu, Fatih Ozaltin, Samiye Yabanoglu-Ciftci, Bora Gulhan, Cemil Can Eylem, Ipek Baysal, Elif Damla Gok-Topak, Kezban Ulubayram, Osman Ugur Sezerman, Gulberk Ucar, Sedef Kir, Rezan Topaloglu
Summary: This study identified candidate biomarkers for the diagnosis and follow-up of cystinosis through multiomics studies. 10 metabolites were found to differ between the patient and control groups in plasma metabolomics analysis, and several metabolites were also significantly different in urine metabolomic analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Obstetrics & Gynecology
J. Rohayem, D. Haffner, J. F. Cremers, S. Huss, J. Wistuba, D. Weitzel, S. Kliesch, K. Hohenfellner
Summary: The study suggests that cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval providing additional opportunities for biological fatherhood. Testicular degeneration in cystinosis may result from lysosomal overload of Sertoli and Leydig cells, and good adherence to cysteamine treatment may delay but not prevent this degeneration. Endocrine testicular function in INC may remain compensated until the fourth decade of life, with azoospermia potentially occurring during adolescence.
HUMAN REPRODUCTION
(2021)
Article
Genetics & Heredity
Emma Hector, Donald Cairns, G. Michael Wall
Summary: This study evaluated N-acetylcysteine amide (NACA) and (2R,2R ')-3,3 '-disulfanediyl bis(2-acetamidopropanamide) (diNACA) as potential treatments for cystinosis. The results showed that NACA and diNACA were non-toxic to human cystinotic fibroblasts and significantly increased cell viability. Compared to cysteamine, NACA exhibited a more rapid and greater potency in cystine reduction.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Cell Biology
Katharina Hohenfellner, Ewa Elenberg, Gema Ariceta, Galina Nesterova, Neveen A. Soliman, Rezan Topaloglu
Summary: Newborn screening is a successful secondary prevention measure for childhood diseases, allowing for early disease identification and treatment. The introduction of a new target disease requires careful analysis of the screening process, including scientific background, analytics, and logistics. Early diagnosis of nephropathic cystinosis is important, and molecular technologies have shown feasibility for its screening.
Review
Cell Biology
Francesco Emma, Giovanni Montini, Marco Pennesi, Licia Peruzzi, Enrico Verrina, Bianca Maria Goffredo, Fabrizio Canalini, David Cassiman, Silvia Rossi, Elena Levtchenko
Summary: Early diagnosis and effective therapy are crucial for the prognosis and quality of life of patients with nephropathic cystinosis. Accurate monitoring of intracellular cystine concentration is essential for successful treatment. Cystine depletion is the only available treatment and should be started immediately to slow down organ damage. New biomarkers play a significant role in disease management, from diagnosis to treatment.
Article
Genetics & Heredity
K. V. Savostyanov, A. A. Pushkov, O. A. Shchagina, V. V. Maltseva, E. A. Suleymanov, I. S. Zhanin, N. N. Mazanova, A. P. Fisenko, P. S. Mishakova, A. V. Polyakov, E. V. Balanovska, R. A. Zinchenko, A. N. Tsygin
Summary: Nephropathic cystinosis is a rare genetic disorder caused by biallelic mutations in the CTNS gene, resulting in the accumulation of the amino acid cystine. This study analyzed the clinical, biochemical, and molecular genetic characteristics of 40 Russian patients with CTNS gene mutations and found that the 57 kb deletion was the most common pathogenic variant.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Amer Jamalpoor, Charlotte A. G. H. van Gelder, Fjodor A. Yousef Yengej, Esther A. Zaal, Sante P. Berlingerio, Koenraad R. Veys, Carla Pou Casellas, Koen Voskuil, Khaled Essa, Carola M. E. Ammerlaan, Laura Rita Rega, Reini E. N. van der Welle, Marc R. Lilien, Maarten B. Rookmaaker, Hans Clevers, Judith Klumperman, Elena Levtchenko, Celia R. Berkers, Marianne C. Verhaar, Maarten Altelaar, Rosalinde Masereeuw, Manoe J. Janssen
Summary: Through omics analysis, researchers identified alpha-ketoglutarate as a potential metabolite linking cystinosin loss to autophagy, apoptosis, and kidney proximal tubule impairment in cystinosis. Combining this insight with a drug screen, they discovered that a bicalutamide-cysteamine combination treatment could correct the phenotype of cystinotic kidney proximal tubule cells.
EMBO MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Marya Bengali, Spencer Goodman, Xiaoying Sun, Magdalene A. Dohil, Ranjan Dohil, Robert Newbury, Tatiana Lobry, Laura Hernandez, Corinne Antignac, Sonia Jain, Stephanie Cherqui
Summary: This study developed a noninvasive imaging method to quantify dermal cystine crystal accumulation in cystinosis patients. Results showed increased nCCV in patients compared to controls. nCCV levels correlated with various clinical outcomes, suggesting it may be used as a potential new biomarker for monitoring cystinosis.
Article
Multidisciplinary Sciences
Jun Ohta
Summary: The Calvin-Benson cycle is the most important metabolic pathway for CO2 fixation and involves various intermediates. A recent study has discovered a novel variant of this cycle that bypasses fructose 1,6-bisphosphate (FBP), offering a simpler explanation for previous findings.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Cell Biology
Jerry Schneider, Elena Levtchenko
Summary: This article describes the remarkable contributions of Dr. Jerry Schneider, an American physician and scientist, in the field of cystinosis research. Starting from his seminal Science paper, Dr. Schneider led a research team in understanding the pathogenesis of cystinosis and finding treatments for this devastating disease. His personal history highlighted the major milestones in cystinosis research, serving as an inspiration and guide for young doctors and scientists continuing the quest for a cure.
Review
Pediatrics
Tjessa Bondue, Lambertus van den Heuvel, Elena Levtchenko, Roland Brock
Summary: Inherited kidney diseases affect different nephron segments and can lead to kidney failure. Advances in genetic testing have increased our understanding of the molecular basis and pathophysiology of these diseases, revealing new potential therapeutic targets. RNA-based therapies, which have revolutionized molecular therapy, are now emerging in the field of kidney diseases.
PEDIATRIC NEPHROLOGY
(2023)
Editorial Material
Cell Biology
Jerry Schneider, Elena Levtchenko
Summary: This article describes the remarkable contributions of Dr. Jerry Schneider, an American physician and scientist, in the field of cystinosis research. Starting from his seminal Science paper, Dr. Schneider led a research team in understanding the pathogenesis of cystinosis and finding treatments for this devastating disease. His personal history highlighted the major milestones in cystinosis research, serving as an inspiration and guide for young doctors and scientists continuing the quest for a cure.
Article
Cell Biology
Koenraad Veys, Sante Princiero Berlingerio, Dries David, Tjessa Bondue, Katharina Held, Ahmed Reda, Martijn van den Broek, Koen Theunis, Mirian Janssen, Elisabeth Cornelissen, Joris Vriens, Francesca Diomedi-Camassei, Rik Gijsbers, Lambertus van den Heuvel, Fanny O. Arcolino, Elena Levtchenko
Summary: In this study, kidney progenitor cells (KPCs) were found in the urine of cystinosis patients, which have the potential for regeneration and can differentiate into functional cells. Gene addition using lentiviral vector technology was effective in reducing cystine levels. This finding provides a novel tool for disease modeling.
Article
Biochemistry & Molecular Biology
Nikolaos G. Bliziotis, Leo A. J. Kluijtmans, Gerjen H. Tinnevelt, Parminder Reel, Smarti Reel, Katharina Langton, Mercedes Robledo, Christina Pamporaki, Alessio Pecori, Josie Van Kralingen, Martina Tetti, Udo F. H. Engelke, Zoran Erlic, Jasper Engel, Timo Deutschbein, Svenja Noelting, Aleksander Prejbisz, Susan Richter, Jerzy Adamski, Andrzej Januszewicz, Filippo Ceccato, Carla Scaroni, Michael C. Dennedy, Tracy A. Williams, Livia Lenzini, Anne-Paule Gimenez-Roqueplo, Eleanor Davies, Martin Fassnacht, Hanna Remde, Graeme Eisenhofer, Felix Beuschlein, Matthias Kroiss, Emily Jefferson, Maria-Christina Zennaro, Ron A. Wevers, Jeroen J. Jansen, Jaap Deinum, Henri J. L. M. Timmers
Summary: This study aimed to establish signatures for different forms of endocrine hypertension (EHT) and investigate unbiased disease biomarkers. Plasma samples from 13 biobanks across seven countries were analyzed using untargeted NMR metabolomics. While signatures that could differentiate different forms of EHT were found, confounding effects related to sample center and age were also identified. Various approaches were applied to correct these confounding effects, but no biomarkers for differentiating primary hypertension from EHT could be identified.
Article
Endocrinology & Metabolism
Koenraad Veys, Ward Zadora, Katharina Hohenfellner, Detlef Bockenhauer, Mirian C. H. Janssen, Patrick Niaudet, Aude Servais, Rezan Topaloglu, Martine Besouw, Robert Novo, Dieter Haffner, Nele Kanzelmeyer, Lars Pape, Elke Wuhl, Erik Harms, Atif Awan, Przemyslaw Sikora, Gema Ariceta, Bert van den Heuvel, Elena Levtchenko
Summary: In infantile nephropathic cystinosis, presymptomatic treatment with cysteamine improves the renal outcome, which justifies the inclusion of cystinosis into newborn screening programs.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Pediatrics
Lale Sever, Gulseren Pehlivan, Nur Canpolat, Seha Saygili, Ayse Agbas, Ebru Demirgan, Jun Oh, Elena Levtchenko, Dymtro D. Ivanov, Rukshana Shroff
Summary: Pediatric patients on kidney replacement therapy are highly vulnerable during disasters due to limitations in dialysis treatments and shortage of medical resources. Proper measures and support are crucial to mitigate risks and provide necessary care.
PEDIATRIC NEPHROLOGY
(2023)
Article
Pediatrics
Liselotte Van Loo, Karel Allegaert, Elena Levtchenko, Zhenyu Zhang, Jan A. Staessen, Anke Raaijmakers
Summary: This study investigated endothelial integrity in healthy controls and extremely low birth weight (ELBW) survivors. The results suggest that perfused boundary region (PBR) may not be a suitable biomarker for endothelial integrity in ELBW survivors, despite observations of changes in blood pressure and vascularization. These findings highlight the importance of studying and understanding the complex structure of the endothelial glycocalyx in ELBW survivors.
PEDIATRIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tjessa Bondue, Anas Kouraich, Sante Princiero Berlingerio, Koenraad Veys, Sandrine Marie, Khaled O. Alsaad, Essam Al-Sabban, Elena Levtchenko, Lambertus van den Heuvel
Summary: Cystinosis is an autosomal recessive lysosomal storage disease caused by CTNS gene mutations, leading to cystine accumulation in multiple organs. The diagnosis of cystinosis is currently based on elevated white blood cell (WBC) cystine levels. We present a case of adolescent proteinuria and corneal cystine crystals with slightly elevated WBC cystine levels, which hindered the diagnosis of nephropathic cystinosis. However, further examination of skin fibroblasts and urine-derived kidney cells revealed higher cystine levels, along with the presence of a homozygous missense mutation in the CTNS gene. This highlights the importance of considering alternative diagnostic methods for patients with low WBC cystine levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pediatrics
Oyindamola C. C. Adebayo, Agathe B. B. Nkoy, Lambertus P. P. van den Heuvel, Veerle Labarque, Elena Levtchenko, Pierre Delanaye, Hans Pottel
Summary: This review explores the pathophysiological mechanisms of GHF in relation to various clinical conditions in the pediatric population. It discusses the role and mechanism of action of important factors such as gender, low birth weight, and race in the pathogenesis of GHF. Furthermore, it highlights the consequences of GHF in the progression of kidney disease.
PEDIATRIC NEPHROLOGY
(2023)
Review
Pediatrics
Agathe B. Nkoy, Pepe M. Ekulu, Veerle Labarque, Lambertus P. van den Heuvel, Elena N. Levtchenko
Summary: HIV infection remains a significant health threat globally, especially in children living in resource-limited settings. Limited access to ART in sub-Saharan Africa puts HIV-infected children at risk of developing HIVAN without appropriate treatment.
PEDIATRIC NEPHROLOGY
(2023)
Editorial Material
Pediatrics
Ana Teixeira, Rezan Topaloglu, Pierre Cochat, Rosanna Coppo, Elena Levtchenko, Dieter Haffner, John D. Mahan, Jun Oh
PEDIATRIC NEPHROLOGY
(2023)
Article
Pediatrics
Elke De Bruyne, Lore Willem, Koen Van Hoeck, Sarah Reynaert, Sylvie Vankerckhove, Brigitte Adams, Stephanie Leroi, Laure Collard, Aline Michaux, Nathalie Godefroid, Djalila Mekahli, Noel Knops, Sunny Eloot, Ann Raes, Johan Vande Walle, Eline Van Hoecke, Evelien Snauwaert, Elena Levtchenko
Summary: This study investigated the quality of life and illness-related parental stress in children with kidney diseases. The results showed lower quality of life and higher parental stress in pediatric transplant patients compared with non-transplants. These findings highlight the importance of multidisciplinary care for children with kidney diseases, with special attention to transplant patients and their parents.
PEDIATRIC NEPHROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tjessa Bondue, Sante Princiero Berlingerio, Lambertus van den Heuvel, Elena Levtchenko
Summary: mRNA-based therapeutics have shown great potential in vaccination and clinical trials for genetic diseases. Zebrafish embryonic disease models have proven to be valuable for drug testing and can serve as a useful intermediate step before testing in rodent models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Melanie T. Achleitner, Judith J. M. Jans, Laura Ebner, Johannes Spenger, Vassiliki Konstantopoulou, Rene G. Feichtinger, Karin Brugger, Doris Mayr, Ron A. Wevers, Christian Thiel, Saskia B. Wortmann, Johannes A. Mayr
Summary: Two siblings showed increased levels of galactose and related metabolites in neonatal screening, but diagnostic tests did not identify abnormalities in known disease-causing enzymes. Whole-exome sequencing revealed a homozygous missense variant in the PPA1 gene, which was found to reduce enzyme activity and protein stability. The observed metabolic derangement is hypothesized to be a mild manifestation of PPA1 deficiency.
Correction
Biochemistry & Molecular Biology
Shona Kalkman, Ron A. Wevers, Frits A. Wijburg, Mariska M. G. Leeflang
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
