Review
Biochemistry & Molecular Biology
Muna Abed Rabbo, Yara Khodour, Laurie S. Kaguni, Johnny Stiban
Summary: Sphingolipids and their metabolism have become a hotly debated topic in various biochemical fields, impacting health and causing genetic sphingolipid storage diseases. These diseases mainly affect the neuronal and immune systems, with potential therapeutic strategies being discussed in this review.
LIPIDS IN HEALTH AND DISEASE
(2021)
Article
Health Care Sciences & Services
Franklin Ducatez, Wladimir Mauhin, Agnes Boullier, Carine Pilon, Tony Pereira, Raphael Aubert, Olivier Benveniste, Stephane Marret, Olivier Lidove, Soumeya Bekri, Abdellah Tebani
Summary: Fabry disease is an X-linked lysosomal disorder with complex genetics and organ damage. Metabolomics can identify distinct metabolic patterns, reveal disease characteristics, and establish predictive models, contributing to a deeper understanding of the disease mechanisms.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Endocrinology & Metabolism
Laura A. Adang, Samar Mowafy, Zackary M. Herbst, Zitao Zhou, Lars Schlotawa, Karthikeyan Radhakrishnan, Brenna Bentley, Vi Pham, Emily Yu, Nishitha R. Pillai, Paul J. Orchard, Mauricio De Castro, Adeline Vanderver, Marzia Pasquali, Michael H. Gelb, Rebecca C. Ahrens-Nicklas
Summary: This study evaluates residual sulfatase activity and GAG accumulation in multiple sulfatase deficiency (MSD) patients, and finds that different sulfatases have different tolerance to activation by formylglycine generating enzyme (FGE). Moreover, specific urinary GAG subspecies accumulation patterns can serve as biomarkers for disease severity. These findings provide important insights into sulfatase regulation and offer much-needed biomarkers for upcoming clinical trials.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Maria del Pilar Chantada-Vazquez, Susana B. Bravo, Sofia Barbosa-Gouveia, Jose V. Alvarez, Maria L. Couce
Summary: Inherited metabolic disorders (IMDs) are rare medical conditions caused by genetic defects that affect the body's metabolism. Early diagnosis and understanding of the disease are crucial, and proteomics and tandem mass spectrometry (MS/MS) have emerged as valuable tools for studying IMDs. Proteomics can aid in the identification of biomarkers, early diagnosis, and better understanding of the underlying pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Benedicte Sudrie-Arnaud, Sarah Snanoudj, Ivana Dabaj, Helene Dranguet, Lenaig Abily-Donval, Axel Lebas, Myriam Vezain, Benedicte Heron, Isabelle Marie, Marc Duval-Arnould, Stephane Marret, Abdellah Tebani, Soumeya Bekri
Summary: Diagnosis of lysosomal disorders can be challenging due to their clinical heterogeneity and overlapping phenotypes. A newly developed capture-based NGS panel allows for efficient detection of genetic variations associated with LDs, potentially improving diagnostic speed and accuracy. This advanced sequencing approach, combined with bioinformatics analyses, offers a cost-effective method for identifying causative variants in lysosomal disorders.
Review
Medicine, General & Internal
Paola Jacqueline Velez Pinos, Michell Susan Saavedra Palacios, Paolo Andres Colina Arteaga, Diciana Arevalo Cordova
Summary: Niemann-Pick disease (NPD) A/B is a lysosomal storage disease caused by a variation in SMPD1. The diagnosis of the atypical case was made at four years and three months of age. A variety of tests were conducted to confirm the diagnosis, including enzyme activity study, liver and bone marrow biopsies, and molecular studies. Diagnosis is crucial due to the multisystem involvement of this LSD.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ivan Bradic, Laura Liesinger, Katharina B. Kuentzel, Nemanja Vujic, Michael Trauner, Ruth Birner-Gruenberger, Dagmar Kratky
Summary: Lysosomal acid lipase (LAL) is responsible for degrading cholesteryl esters and triacylglycerols at acidic pH. Impaired LAL activity leads to LAL deficiency and non-alcoholic fatty liver disease (NAFLD). Comprehensive proteomic profiling of mouse livers with systemic or hepatocyte-specific loss of LAL revealed drastic proteome alterations in Lal-/- mice, including dysregulation of metabolism, inflammation, liver fibrosis, and cancer-related proteins. In contrast, hepLal-/- mice showed minor changes in the liver proteome, suggesting that loss of LAL solely in hepatocytes does not phenocopy the metabolic alterations observed in mice lacking LAL globally.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Gilian Guerreiro, Marion Deon, Carmen Regla Vargas
Summary: Lysosomal acid lipase deficiency (LALD) is a metabolic disorder without effective treatment. This study investigated parameters of oxidative and inflammatory stress in LALD patients, revealing the role of reactive species and inflammation in the pathophysiology of this disorder. The findings suggest potential benefits of antioxidant and anti-inflammatory substances as adjuvant tools in the treatment of LALD.
BIOCHEMISTRY AND CELL BIOLOGY
(2023)
Article
Nutrition & Dietetics
Meriah S. Schoen, Usha Ramakrishnan, Jessica A. Alvarez, Thomas R. Ziegler, Xiangqin Cui, Rani H. Singh
Summary: This study compared choline consumption among individuals with phenylketonuria (PKU) to a reference sample and identified factors that may affect choline needs. The findings suggest that only a small percentage of PKU patients achieve adequate choline intake, and treatment methods can impact choline levels. Without fortified medical foods, choline and other related nutrient intake may be reduced. Regular monitoring of choline intake and increased fortification of medical foods could benefit this population.
Review
Endocrinology & Metabolism
Zackary M. Herbst, Xinying Hong, Martin Sadilek, Maria Fuller, Michael H. Gelb
Summary: Newborn screening for mucopolysaccharidoses can be done by measuring enzymatic activities or accumulated substances in dried blood spots. Both approaches provide acceptable solutions for screening, but the enzyme-first approach allows for better multiplexing.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Fatih Ezgu
Summary: Sebelipase alfa has been shown to be a safe treatment for lysosomal acid lipase deficiency, with documented adverse events mainly occurring as infusion reactions that are generally mild to moderate and easily managed. Rare cases of anaphylaxis have been reported but successfully treated. The therapy has been effective in changing the natural history of the disease.
EXPERT OPINION ON DRUG SAFETY
(2022)
Article
Biology
Peter M. Masschelin, Pradip Saha, Scott A. Ochsner, Aaron R. Cox, Kang Ho Kim, Jessica B. Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L. Lorenzi, Alli M. Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D. Moore, Scott A. Summers, Neil J. McKenna, Sean M. Hartig
Summary: Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions for cellular energy demands. Depleting FAD pools in mice causes phenotypes associated with organic acidemias and other inborn errors of metabolism (IEMs), such as reduced body weight, hypoglycemia, and fatty liver disease. The study reveals that B2D inhibits fasting activation of PPAR alpha target genes and downregulates gluconeogenesis genes. Knockdown of PPAR alpha in the liver recapitulates B2D effects, while treatment with the PPAR alpha agonist fenofibrate rescues fasting glucose availability and overcomes B2D phenotypes.
Article
Biochemistry & Molecular Biology
Daphne E. Boer, Mina Mirzaian, Maria J. Ferraz, Kimberley C. Zwiers, Merel Baks, Marc D. Hazeu, Roelof Ottenhoff, Andre R. A. Marques, Rianne Meijer, Jonathan C. P. Roos, Timothy M. Cox, Rolf G. Boot, Navraj Pannu, Herman S. Overkleeft, Marta Artola, Johannes M. Aerts
Summary: Deficiency of glucocerebrosidase (GBA) causes Gaucher disease due to its complex catalytic functions, not only playing a key role in transglycosylation reactions, but also cleaving beta-xylosides. Patients with Gaucher disease have reduced GBA activity, leading to impaired related reactions.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yupeng Liu, Zhehui Chen, Lulu Kang, Ruxuan He, Jinqing Song, Yi Liu, Chunyan Shi, Junya Chen, Hui Dong, Yao Zhang, Yanyan Ma, Tongfei Wu, Qiao Wang, Yuan Ding, Xiyuan Li, Dongxiao Li, Mengqiu Li, Ying Jin, Jiong Qin, Yanling Yang
Summary: In this study, the accuracy of prenatal diagnosis of MMA was increased by using amniotic fluid biochemical assays using GC/MS and LC/MS/MS in parallel. Propionylcarnitine was found to be a more reliable marker than methylmalonic acid in amniotic fluid. Total homocysteine (tHcy) is recommended for the prenatal diagnosis of combined MMA and homocysteinemia.
Article
Genetics & Heredity
Sarah Debs, Carlos R. Ferreira, Catherine Groden, H. Jeffrey Kim, Kelly A. King, Monique C. King, Tanya Lehky, Edward W. Cowen, Laura H. Brown, Melissa Merideth, Carter M. Owen, Ellen Macnamara, Camilo Toro, William A. Gahl, Ariane Soldatos
Summary: A woman with a rare phosphoserine aminotransferase deficiency was successfully treated with high dose oral L-serine, resulting in complete resolution of ichthyosis. Early diagnosis and treatment are crucial in halting neurodegeneration progression and improving neurological disabilities.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Julian Kirchner, Benedikt M. Schaarschmidt, Firas Kour, Lino M. Sawicki, Ole Martin, Johannes Bode, Stephan vom Dahl, Verena Keitel, Dieter Haeussinger, Christina Antke, Christian Buchbender, Gerald Antoch, Philipp Heusch
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2020)
Article
Medicine, General & Internal
Verena Keitel, Stephan vom Dahl, Dieter Haeussinger
DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
(2020)
Article
Endocrinology & Metabolism
Sofiya Gancheva, Daria Caspari, Alessandra Bierwagen, Tomas Jelenik, Sonia Caprio, Nicola Santoro, Maik Rothe, Daniel F. Markgraf, Diran Herebian, Jong-Hee Hwang, Soner Oener-Sieben, Jasmin Mennenga, Giovanni Pacini, Eva Thimm, Andrea Schlune, Thomas Meissner, Stephan vom Dahl, Dirk Klee, Ertan Mayatepek, Michael Roden, Regina Ensenauer
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Review
Endocrinology & Metabolism
Eline C. B. Eskes, Barbara Sjouke, Frederic M. Vaz, Susan M. I. Goorden, Andre B. P. van Kuilenburg, Johannes M. F. G. Aerts, Carla E. M. Hollak
MOLECULAR GENETICS AND METABOLISM
(2020)
Article
Genetics & Heredity
Simon Korver, Gert J. Geurtsen, Carla E. M. Hollak, Ivo N. van Schaik, Maria G. F. Longo, Marjana R. Lima, Leonardo Vedolin, Marcel G. W. Dijkgraaf, Mirjam Langeveld
ORPHANET JOURNAL OF RARE DISEASES
(2020)
Article
Genetics & Heredity
Mendy M. Welsink-Karssies, Kim J. Oostrom, Merel E. Hermans, Carla E. M. Hollak, Mirian C. H. Janssen, Janneke G. Langendonk, Esmee Oussoren, M. Estela Rubio Gozalbo, Maaike ee Vries, Gert J. Geurtsen, Annet M. Bosch
ORPHANET JOURNAL OF RARE DISEASES
(2020)
Article
Nutrition & Dietetics
Friederike Barhold, Uta Meyer, Anne-Kathrin Neugebauer, Eva Maria Thimm, Dinah Lier, Stefanie Rosenbaum-Fabian, Ulrike Och, Anna Fekete, Dorothea Moslinger, Carmen Rohde, Skadi Beblo, Michel Hochuli, Nina Bogovic, Vanessa Korpel, Stephan vom Dahl, Sebene Mayorandan, Aleksandra Fischer, Peter Freisinger, Katharina Dokoupil, Margret Heddrich-Ellerbrok, Monika Jorg-Streller, Agnes van Teeffelen-Heithoff, Janina Lahl, Anibh Martin Das
Summary: A retrospective study evaluating the impact of a simplified diet on patients with tyrosinaemia type 1 showed increased tyrosine and phenylalanine blood concentrations without the need to weigh food. Compliance with dietary recommendations was higher with the simplified diet, indicating that patient adherence plays a significant role in metabolic control. Further prospective studies with larger sample sizes are needed for a better understanding of the effects of dietary recommendations on metabolic control.
Article
Cardiac & Cardiovascular Systems
Mohamed El Sayed, Alexander Hirsch, Matthijs Boekholdt, Laura van Dussen, Mareen Datema, Carla Hollak, Mirjam Langeveld
Summary: The study demonstrates that sex and disease phenotype significantly influence the risk and age of onset of cardiac events in patients with Fabry disease (FD), highlighting the importance of patient-specific follow-up and treatment.
Review
Gastroenterology & Hepatology
Roman Liebe, Irene Esposito, Hans H. Bock, Stephan vom Dahl, Jan Stindt, Ulrich Baumann, Tom Luedde, Verena Keitel
Summary: The term NAFLD was originally used to describe hepatic fat deposition in association with the metabolic syndrome. Secondary causes of fatty liver disease should be considered during diagnosis and treatment to halt disease progression, while genetic variants may play a role in the development and progression of liver diseases.
JOURNAL OF HEPATOLOGY
(2021)
Article
Economics
Sandra M. Sirrs, Marie-Francoise Arthus, Daniel G. Bichet, Cheryl Rockman-Greenberg, Kaye LeMoine, Chantal F. Morel, Robin Lachmann, Larry D. Lynd, Syed Wasim, Michael L. West, Carla Hollak
Summary: Analysis of data from the Canadian Fabry Disease Initiative showed that establishing an independent registry for ongoing postauthorization surveillance of orphan medicinal products is cost-effective and efficient, with higher data completeness. 77% of patients continued to enroll in the registry even after enrollment ceased to be a requirement for therapy, indicating patient acceptance of the structure.
Editorial Material
Medicine, General & Internal
C. E. M. Hollak
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Economics
Sibren van den Berg, Vincent van der Wel, Saco J. de Visser, Bas C. Stunnenberg, Lonneke Timmers, Martijn H. van der Ree, Pieter G. Postema, Carla E. M. Hollak
Summary: Mexiletine is a drug initially used for arrhythmias, but later repurposed for NDM patients. Recent price increases in Europe led to discussions on affordability. A cost-based pricing model was used to calculate a fair price for Mexiletine, with results showing a significant difference from the current list price.
Article
Gastroenterology & Hepatology
Sven H. Loosen, Anselm Kunstein, Stephan vom Dahl, Johannes G. Bode, Tom Luedde, Jennis Kandler
ENDOSCOPY INTERNATIONAL OPEN
(2022)
Article
Endocrinology & Metabolism
Karina Grohmann-Held, Peter Burgard, Christoph G. O. Baerwald, Skadi Beblo, Stephan vom Dahl, Anibh Das, Katharina Dokoupil, Sandra Fleissner, Peter Freisinger, Margret Heddrich-Ellerbrok, Alexandra Jung, Vanessa Korpel, Johannes Kraemer, Dinah Lier, Esther M. Maier, Uta Meyer, Chris Muehlhausen, Martha Newger, Ulrike Och, Ursula Ploeckinger, Stefanie Rosenbaum-Fabian, Frank Rutsch, Rene Santer, Petra Schick, Martin Schwarz, Ute Spiekerkoetter, Ursula Strittmatter, Alena G. Thiele, Athanasia Ziagaki, Ulrike Muetze, Florian Gleich, Sven F. Garbade, Stefan Koelker
Summary: This study evaluated the feasibility and effectiveness of treatment recommendations for pregnant women with phenylketonuria (PKU) and identified factors influencing maternal metabolic control and children's outcome. Good metabolic control during pregnancy is crucial to prevent maternal PKU syndrome in offspring.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Gastroenterology & Hepatology
Nils Bardeck, Martha Paluschinski, Mirco Castoldi, Claus Kordes, Boris Goerg, Jan Stindt, Tom Luedde, Stephan Vom Dahl, Dieter Haeussinger, David Schoeler
Summary: This study identified microRNA 141-3p as an osmosensitive miRNA that inhibits proliferation during liver cell swelling. Upregulation of microRNA 141-3p, controlled by Src-, Erk-, and p38-MAPK signaling, results in decreased mRNA levels of various genes involved in metabolic processes, macromolecular biosynthesis, and cell cycle progression.
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)