Article
Biochemistry & Molecular Biology
Hans-Otto Bohm, Mazyar Yazdani, Elise Mork Sandas, Anja Osteby Vassli, Erle Kristensen, Helge Rootwelt, Hanne Bendiksen Skogvold, Eylert Brodtkorb, Katja Benedikte Presto Elgstoen
Summary: This study used global metabolomics to analyze plasma samples from patients with PDE-ALDH7A1 and identified two novel and reliable pyridoxine-independent diagnostic markers. The study also proposed a possible reaction mechanism for one of the markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Xianru Jiao, Pan Gong, Ye Wu, Yuehua Zhang, Zhixian Yang
Summary: Patients from the same family often exhibit similar phenotypes, including onset age and seizure type. Early treatment with pyridoxine and infrequent seizures have a positive relationship with prognosis. Deletions in exon 1 and exon 8-13 may be associated with a severe phenotype.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Xianru Jiao, Pan Gong, Yue Niu, Yuehua Zhang, Zhixian Yang
Summary: This study analyzed the clinical features, treatment, and prognosis of epileptic spasms in patients with vitamin B6-dependent epilepsy caused by different gene mutations. The results showed that epileptic spasms were a common presentation, and the treatment and prognosis varied among patients with different gene mutations.
FRONTIERS IN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
David A. Korasick, John J. Tanner
Summary: Certain mutations in the ALDH7A1 gene cause pyridoxine-dependent epilepsy (PDE), characterized by seizures and sometimes intellectual disability. These mutations, including over 70 missense mutations, have complex effects on the structure and catalytic activity of ALDH7A1. Mutations targeting active site residues and those remote from the site show varied impact, indicating the challenge in predicting the effects of missense mutations on enzyme function. Additional biophysical analyses of disease-causing mutations are necessary to develop predictive rules for enzyme structure and function.
Article
Endocrinology & Metabolism
Rojan Ipek, Busra Eser Cavdartepe, Deniz Kor, Cetin Okuyaz
Summary: Seizures in newborn infants may indicate hereditary metabolic diseases, such as pyridoxine-dependent epilepsy (PDE). PDE is a treatable disorder that is resistant to traditional antiepileptic drugs but responds dramatically to high-dose pyridoxine. This case report highlights the importance of considering pyridoxine dependence in the differential diagnosis of epilepsy patients.
METABOLIC BRAIN DISEASE
(2022)
Review
Pediatrics
Flavia Maria Consuelo La Mendola, Tiziana Timpanaro, Daniela Caruso, Maria Teresa Garozzo, Santiago Presti, Catia Romano, Elena R. Pratico, Giulia Lombardo, Antonio Zanghi, Raffaele Falsaperla
Summary: Despite traditionally being associated with mutations in SLC2A1 genes, it has been found that mutations in ALDH7A1 can also cause pyridoxine-dependent epilepsy (PDE). PDE can be classified into classical and atypical forms, with the classical form showing early onset seizures and responsiveness to pyridoxine therapy.
JOURNAL OF PEDIATRIC NEUROLOGY
(2021)
Article
Clinical Neurology
M. Strijker, L. A. Tseng, L. K. van Avezaath, M. A. M. Oude Luttikhuis, T. Ketelaar, C. R. Coughlin, M. A. Coenen, F. J. van Spronsen, M. Williams, M. C. de Vries, H. E. Westerlaan, L. A. Bok, C. D. M. van Karnebeek, R. J. Lunsing
Summary: This study explores the cognitive and neurological features of Dutch PDE-ALDH7A1 cohort, finding a wide range of outcomes in terms of neurological function and intelligence quotient. While lysine reduction therapy (LRT) shows potential benefits, more research is needed due to heterogeneous data in small patient numbers. Additionally, a portion of patients still exhibit normal neurological exams and IQ levels.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2021)
Article
Neurosciences
Konrad Kaminiow, Magdalena Pajak, Renata Pajak, Justyna Paprocka
Summary: Pyridoxine-dependent epilepsy (PDE) is a neurometabolic disorder caused by a deficiency of alpha-aminoadipic semialdehyde dehydrogenase, leading to seizure episodes that are responsive to vitamin B6 supplementation. Diagnosis and treatment of PDE can be challenging due to its rarity and delayed onset of seizures.
Article
Genetics & Heredity
Maria E. Morales, Tiffany Kaul, JaNiece Walker, Chelsea Everett, Travis White, Prescott Deininger
Summary: Alu elements, the most abundant source of nonallelic homology in the human genome, play a crucial role in genetic instability. Alu mismatches influence various DNA recombination processes, leading to deletions with different mechanisms depending on DNA repair defects.
Article
Pediatrics
Giulia Aquilano, Agnes Linner, Sofia Ygberg, Tommy Stoedberg, Ewa Henckel
Summary: Pyridoxine-dependent epilepsy is a rare autosomal recessive disease predominantly occurring in neonates, characterized by seizures unresponsive to common antiseizure medications but controllable with pyridoxine administration. It can be initially misdiagnosed or delayed due to symptoms resembling common neonatal disorders.
FRONTIERS IN PEDIATRICS
(2022)
Article
Endocrinology & Metabolism
Curtis R. Coughlin, Laura A. Tseng, Jose E. Abdenur, Catherine Ashmore, Francois Boemer, Levinus A. Bok, Monica Boyer, Daniela Buhas, Peter T. Clayton, Anibh Das, Hanka Dekker, Athanasios Evangeliou, Francois Feillet, Emma J. Footitt, Sidney M. Gospe, Hans Hartmann, Majdi Kara, Erle Kristensen, Joy Lee, Rina Lilje, Nicola Longo, Roelineke J. Lunsing, Philippa Mills, Maria T. Papadopoulou, Phillip L. Pearl, Flavia Piazzon, Barbara Plecko, Arushi G. Saini, Saikat Santra, Damayanti R. Sjarif, Sylvia Stockler-Ipsiroglu, Pasquale Striano, Johan L. K. Van Hove, Nanda M. Verhoeven-Duif, Frits A. Wijburg, Sameer M. Zuberi, Clara D. M. van Karnebeek
Summary: Pyridoxine-dependent epilepsy is a rare genetic condition characterized by neurological and developmental abnormalities due to a deficiency of a specific enzyme, treatment includes supplementation of pyridoxine and dietary adjustments to improve patient outcomes.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Pediatrics
Marc Gibaud, Magalie Barth, Jeremie Lefranc, Karine Mention, Nathalie Villeneuve, Manuel Schiff, Helene Maurey, Marie-Anne Barthez, Isabelle Caubel, Mondher Chouchane, Diane Doummar, Manoelle Kossorotoff, Marie-Dominique Lamblin, Agathe Roubertie, Rima Nabbout, Patrick Van Bogaert
Summary: The study characterized the electro-clinical presentation of patients with PDE and PLP-dependent epilepsy, finding that the presentation of these conditions as de novo West syndrome is extremely rare, thus not justifying a systematic trial of pyridoxine or PLP. It is suggested to consider a therapeutic trial with these vitamins in West syndrome if spasms are associated with other seizure types or start before the age of 2 months.
FRONTIERS IN PEDIATRICS
(2021)
Article
Multidisciplinary Sciences
Xiao-Yong Zhan, Jin-Lei Yang, Xuefu Zhou, Yi-Chao Qian, Ke Huang, Honghua Sun, Huacheng Wang, Yang Leng, Bihui Huang, Yulong He
Summary: SidJ family proteins play a crucial role in the virulence of Legionella pneumophila, regulating cellular processes through a unique phosphoribosyl ubiquitination mechanism. The evolution of the sidJ gene is shaped by intragenic recombination and strong positive selection, potentially impacting the balance of ubiquitin ligase activity in different hosts of the bacteria.
Article
Clinical Neurology
Perrine Minet, Catherine Sarret, Ania Miret, Karine Mention, Jean Francois Benoist, Ganaelle Remerand
Summary: Pyridoxine-dependent epilepsy (PDE) is a recessive genetic disease that shows a therapeutic response to pyridoxine treatment, with recent discoveries helping to understand the underlying mechanism. The new triple therapy (TT) approach has shown improvements in epilepsy control and neurodevelopment in patients with PDE, with promising results in clinical evolution.
ACTA NEUROLOGICA BELGICA
(2021)
Article
Biochemistry & Molecular Biology
Hannah Trost, Arianna Merkell, Felicia Wednesday Lopezcolorado, Jeremy M. Stark
Summary: Repeat-mediated deletions (RMDs) are chromosomal rearrangements that result in the loss of sequences between homologous repeats. The mechanisms of RMD suppression and resolution of sequence divergence are poorly understood. In this study, we identified MLH1 as a suppressor of RMDs with sequence divergence, acting in the same pathway as MSH2 and MSH6. We also found that MLH1 promotes directional resolution of sequence divergence in the RMD product, and this polarity is influenced by the MLH1-PMS2 endonuclease.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Endocrinology & Metabolism
Nina Patel, Philippa Mills, James Davison, Maureen Cleary, Paul Gissen, Blerida Banushi, Ivan Doykov, Megan Dorman, Kevin Mills, Wendy E. Heywood
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Clinical Neurology
Sarah M. Dixon, Michael M. Binkley, Sidney M. Gospe, Rejean M. Guerriero
Summary: Recent child neurology residency applicants prioritize quality of life factors over curriculum when selecting a program. As a result, residency programs should focus on fostering interactions with residents during the interview process and promoting resident wellness initiatives throughout training.
PEDIATRIC NEUROLOGY
(2021)
Editorial Material
Clinical Neurology
Pedro Weisleder, Sidney M. Gospe
PEDIATRIC NEUROLOGY
(2020)
Article
Endocrinology & Metabolism
Curtis R. Coughlin, Laura A. Tseng, Jose E. Abdenur, Catherine Ashmore, Francois Boemer, Levinus A. Bok, Monica Boyer, Daniela Buhas, Peter T. Clayton, Anibh Das, Hanka Dekker, Athanasios Evangeliou, Francois Feillet, Emma J. Footitt, Sidney M. Gospe, Hans Hartmann, Majdi Kara, Erle Kristensen, Joy Lee, Rina Lilje, Nicola Longo, Roelineke J. Lunsing, Philippa Mills, Maria T. Papadopoulou, Phillip L. Pearl, Flavia Piazzon, Barbara Plecko, Arushi G. Saini, Saikat Santra, Damayanti R. Sjarif, Sylvia Stockler-Ipsiroglu, Pasquale Striano, Johan L. K. Van Hove, Nanda M. Verhoeven-Duif, Frits A. Wijburg, Sameer M. Zuberi, Clara D. M. van Karnebeek
Summary: Pyridoxine-dependent epilepsy is a rare genetic condition characterized by neurological and developmental abnormalities due to a deficiency of a specific enzyme, treatment includes supplementation of pyridoxine and dietary adjustments to improve patient outcomes.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Jonas Abdel-Khalik, Thomas Hearn, Alison L. Dickson, Peter J. Crick, Eylan Yutuc, Karl Austin-Muttitt, Brian W. Bigger, Andrew A. Morris, Cedric H. Shackleton, Peter T. Clayton, Takashi Iida, Ria Sircar, Rajat Rohatgi, Hanns-Ulrich Marschall, Jan Sjovall, Ingemar Bjorkhem, Jonathan G. L. Mullins, William J. Griffiths, Yuqin Wang
Summary: A newly identified pathway of bile acid biosynthesis in patients with SLOS and pregnancy, involving intermediates that modulate the activity of Smo, an oncoprotein that mediates Hedgehog signaling, may be responsible for some features of SLOS.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Katharina Iwan, Robert Clayton, Philippa Mills, Barbara Csanyi, Paul Gissen, Sara E. Mole, David N. Palmer, Kevin Mills, Wendy E. Heywood
Summary: NCL is a group of rare neurodegenerative disorders characterized by accumulation of cellular storage bodies. Current therapeutic options are limited, but urine biomarkers may help monitor disease progression and treatment response. Through proteomic analysis and a targeted assay, certain proteins were found to be increased in NCL patients, which could be used to monitor the effectiveness of future therapies.
Review
Pediatrics
Rudolf Korinthenberg, Regina Trollmann, Barbara Plecko, Georg M. Stettner, Markus Blankenburg, Joachim Weis, Benedikt Schoser, Wolfgang Mueller-Felber, Nina Lochbuehler, Gabriele Hahn, Sabine Rudnik-Schoeneborn
Summary: This article provides information on differential diagnostic workup for peripheral nerve disorders, developed through a formal consensus process involving experts from 10 German societies dedicated to neuroscience. The guidelines emphasize the importance of patient history and clinical findings in determining further diagnostic steps, including nerve sonography, MRI, and genetic testing for hereditary neuropathies.
Article
Biochemistry & Molecular Biology
Youssef Khalil, Sara Carrino, Fujun Lin, Anna Ferlin, Heena V. Lad, Francesca Mazzacuva, Sara Falcone, Natalie Rivers, Gareth Banks, Danilo Concas, Carlos Aguilar, Andrew R. Haynes, Andy Blease, Thomas Nicol, Raya Al-Shawi, Wendy Heywood, Paul Potter, Kevin Mills, Daniel P. Gale, Peter T. Clayton
Summary: This study demonstrates the powerful insight brought by proteomic and metabolomic profiling of Hacl1(-/-) mice in better understanding disease mechanism in fatty acid alpha-oxidation disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Laura A. Tseng, Jose E. Abdenur, Ashley Andrews, Verena G. Aziz, Levinus A. Bok, Monica Boyer, Daniela Buhas, Hans Hartmann, Emma J. Footitt, Sabine Gronborg, Mirian C. H. Janssen, Nicola Longo, Roelineke J. Lunsing, Alex E. MacKenzie, Frits A. Wijburg, Sidney M. Gospe, Curtis R. Coughlin, Clara D. M. van Karnebeek
Summary: Early initiation of adjunct pyridoxine treatment may improve neurodevelopmental outcomes in patients with PDE-ALDH7A1.
MOLECULAR GENETICS AND METABOLISM
(2022)
Editorial Material
Medical Laboratory Technology
Laura A. Tseng, Udo F. H. Engelke, Marleen C. D. G. Huigen, Leo A. J. Kluijtmans, Charlotte A. Haaxma, David A. Koolen, Levinus A. Bok, Jason N. Wright, Sidney M. Gospe, Mirian C. H. Janssen, Clara D. M. van Karnebeek, Karlien L. M. Coene
CLINICAL CHEMISTRY
(2022)
Editorial Material
Clinical Neurology
Stephen R. Deputy, Yasmin Khakoo, Sidney M. Gospe
PEDIATRIC NEUROLOGY
(2022)
Article
Genetics & Heredity
L. A. Tseng, L. Teela, M. C. Janssen, L. A. Bok, M. A. A. P. Willemsen, R. F. Neuteboom, L. Haverman, S. M. Gospe, C. R. Coughlin, C. D. M. van Karnebeek
Summary: This study aimed to address the knowledge gap about pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency (PDE-ALDH7A1) in adulthood by investigating the clinical data and patient-reported outcomes. The results showed that long-term seizure control was achieved for almost all patients using pyridoxine monotherapy. However, neurological symptoms, intellectual disability, and neuro-imaging abnormalities were commonly present in this patient population. They scored comparable to the general population in terms of ability to participate and satisfaction with social roles, indicating positive functioning.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Clinical Neurology
Apostolos Papandreou, Ivan Doykov, Justyna Spiewak, Nikita Komarov, Stephanie Habermann, Manju A. Kurian, Philippa B. Mills, Kevin Mills, Paul Gissen, Wendy E. Heywood
Summary: This study aimed to improve biomarker discovery in patients with neurometabolic disorders, using Niemann-Pick type C disease (NPC) as a paradigm. The researchers developed a selective intelligent biomarker panel and applied it to a clinically relevant pediatric patient cohort. The panel showed superior performance compared to individual biomarkers and had 100% specificity for NPC.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2022)
Article
Clinical Neurology
Curtis A. Coughlin, Laura A. Tseng, Levinus Bok, Hans Hartmann, Emma Footitt, Pasquale Striano, Brahim M. Tabarki, Roelineke J. Lunsing, Sylvia Stockler-Ipsiroglu, Shanlea Gordon, Johan L. K. Van Hove, Jose E. Abdenur, Monica Boyer, Nicola Longo, Ashley Andrews, Mirian C. H. Janssen, Annemiek van Wegberg, Chitra Prasad, Asuri N. Prasad, Molly M. Lamb, Frits A. Wijburg, Sidney M. Gospe, Clara van Karnebeek
Summary: This study examines the association between LRTs treatment and cognitive outcomes in patients with PDE-ALDH7A1. The results suggest that treatment with pyridoxine and LRTs at any age is associated with mild improvement in developmental testing, while treatment in early infancy is associated with a clinically significant increase in developmental test scores.
Article
Medicine, Research & Experimental
Udo F. H. Engelke, Rianne E. van Outersterp, Jona Merx, Fred A. M. G. van Geenen, Arno van Rooij, Giel Berden, Marleen C. D. G. Huigen, Leo A. J. Kluijtmans, Tessa M. A. Peters, Hilal H. Al-Shekaili, Blair R. Leavitt, Erik de Vrieze, Sanne Broekman, Erwin van Wijk, Laura A. Tseng, Purva Kulkarni, Floris P. J. T. Rutjes, Jasmin Mecinovic, Eduard A. Struys, Laura A. Jansen, Sidney M. Gospe, Saadet Mercimek-Andrews, Keith Hyland, Michel A. A. P. Willemsen, Levinus A. Bok, Clara D. M. van Karnebeek, Ron A. Wevers, Thomas J. Boltje, Jos Oomens, Jonathan Martens, Karlien L. M. Coene
Summary: This study identified a potential biomarker for PDE-ALDH7A1 newborn screening and confirmed its suitability in dried bloodspots. The biomarker was found to accumulate in brain tissue of patients and induce epilepsy-like behavior in a zebrafish model system.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
