Search

Your search keyword '"Blom, Henk J."' showing total 979 results
Start Over Author "Blom, Henk J."
979 results on '"Blom, Henk J."'

2. Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: Four new cases and a review of the evidence

Author

Schwahn, Bernd C, Scheffner, Thomas, Stepman, Hedwig, Verloo, Peter, Das, Anibh M, Fletcher, Janice, Blom, Henk J, Benoist, Jean‐Francois, Barshop, Bruce A, Barea, Jaime J, and Feigenbaum, Annette

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Nutrition, Brain Disorders, Rare Diseases, CBS deficiency, adverse drug effect, betaine, brain edema, encephalopathy, homocystinuria, Clinical sciences
Abstract

CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose.

Published
2020

5. 5,10-methenyltetrahydrofolate synthetase deficiency:An extreme rare defect of folate metabolism in two Dutch siblings

Author

Liepina, Lelde, Smith, Desiree E.C., Huidekoper, Hidde, Zeidler, Shimriet, Wamelink, Mirjam, de Wit, Marie Claire, Wilke, Martina, Ruijter, George, Bierau, Jörgen, Blom, Henk J., Liepina, Lelde, Smith, Desiree E.C., Huidekoper, Hidde, Zeidler, Shimriet, Wamelink, Mirjam, de Wit, Marie Claire, Wilke, Martina, Ruijter, George, Bierau, Jörgen, and Blom, Henk J.

Abstract

Two siblings, presenting with a neurometabolic phenotype, were identified with 5, 10-methenyltetrahydrofolate synthetase (MTHFS) deficiency. Whole genome sequencing in both patients demonstrated an homozygous MTHFS variant NM_006441.3(MTHFS):c.434G > A, p.Arg145Gin, which has been described before. At baseline, both patients showed moderate hyperhomocysteinemia, decreased 5-methyltetrahydrofolate (5MTHF), and increased 5-formyltetrahydrofolate (5-FTHF) in whole blood. In CSF, 5MTHF levels were in the low-normal range and 5-FTHF was strongly increased. In our novel enzyme assay, MTHFS activity was deficient in cultured fibroblasts in both sisters. Oral treatment was initiated with escalating dose of 5-methyltetrahydrofolate (5MTHF) up to 12 mg and hydroxycobalamin 5 mg daily. Plasma homocysteine normalized and 5MTHF became elevated in the blood of both patients. The elevated 5FTHF levels increased further on treatment in blood and CSF. This regimen resulted in some clinical improvement of patient 1. In patient 2, the clinical benefits of 5MTHF supplementation were less obvious. It seems plausible that the alleviation of the deficient 5MTHF levels and normalization of homocysteine in blood are of some clinical benefit. On the other hand, the very high levels of 5FTHF may well be detrimental and may prompt us to decrease the dose of 5MTHF. In addition, we hypothesize that the crippled MTHFS enzyme may destabilize the purinosome, which is presumably not ameliorated by 5MTHF.

Published
2024

6. The Homocystinurias

Author

Walter, John H., Blom, Henk J., Oohashi, Toshitaka, editor, Tsukahara, Hirokazu, editor, Ramirez, Francesco, editor, Barber, Chad L., editor, and Otsuka, Fumio, editor

Published
2019
Full Text
View/download PDF

18. Benchmarking Outlier Detection Methods for Detecting IEM Patients in Untargeted Metabolomics Data

Author

Bongaerts, Michiel (author), Kulkarni, Purva (author), Zammit, Alan (author), Bonte, Ramon (author), Kluijtmans, Leo A. J. (author), Blom, Henk J. (author), Engelke, Udo F. H. (author), Tax, D.M.J. (author), Ruijter, George J.G. (author), Reinders, M.J.T. (author), Bongaerts, Michiel (author), Kulkarni, Purva (author), Zammit, Alan (author), Bonte, Ramon (author), Kluijtmans, Leo A. J. (author), Blom, Henk J. (author), Engelke, Udo F. H. (author), Tax, D.M.J. (author), Ruijter, George J.G. (author), and Reinders, M.J.T. (author)

Abstract

Untargeted metabolomics (UM) is increasingly being deployed as a strategy for screening patients that are suspected of having an inborn error of metabolism (IEM). In this study, we examined the potential of existing outlier detection methods to detect IEM patient profiles. We benchmarked 30 different outlier detection methods when applied to three untargeted metabolomics datasets. Our results show great differences in IEM detection performances across the various methods. The methods DeepSVDD and R-graph performed most consistently across the three metabolomics datasets. For datasets with a more balanced number of samples-to-features ratio, we found that AE reconstruction error, Mahalanobis and PCA reconstruction error also performed well. Furthermore, we demonstrated the importance of a PCA transform prior to applying an outlier detection method since we observed that this increases the performance of several outlier detection methods. For only one of the three metabolomics datasets, we observed clinically satisfying performances for some outlier detection methods, where we were able to detect 90% of the IEM patient samples while detecting no false positives. These results suggest that outlier detection methods have the potential to aid the clinical investigator in routine screening for IEM using untargeted metabolomics data, but also show that further improvements are needed to ensure clinically satisfying performances., Pattern Recognition and Bioinformatics

Published
2023
Full Text
View/download PDF

19. Colaboradores

Author

Abrams, Charles S., Adler, Ronald S., Agarwal, Anupam, Akin, Cem, Aksamit, Allen J., Jr., Al-Awqati, Qais, Allen, Upton D., Allos, Ban Mishu, Angus, Derek C., Appelbaum, Frederick R., Armitage, James O., Armstrong, April W., Armstrong, Deborah K., Arnaout, M. Amin, Arnold, Robert M., Aronson, Louise, Atkinson, John P., Attia, Evelyn, Auerbach, Andrew D., Ayanian, John Z., Baddour, Larry M., Baden, Lindsey R., Bailey, Thomas C., Bain, Barbara J., Bajorin, Dean F., Baloh, Robert W., Bangham, Charles R.M., Barasch, Jonathan, Barrett, Bruce, Bartholomew, John R., Bartleson, J.D., Barton, Mary B., Basner, Robert C., Bass, Adam J., Bass, Anne R., Bauman, Julie E., Bausch, Daniel G., Bayer, Arnold S., Bazarian, Jeffrey J., Bearman, Gonzalo M., Becker, Richard C., Beckham, J. David, Beckman, Joshua A., Beigel, John H., Bel, Elisabeth H., Belda, Walter, Jr., Benarroch, Eduardo E., Berger, Joseph R., Berliner, Nancy, Bernat, James L., Bessesen, Daniel H., Bibbins-Domingo, Kirsten, Biesecker, Leslie G., Biundo, Joseph J., Blankson, Joel N., Bloch, Karen C., Blom, Henk J., Boden, William E., Boivin, Guy, Bolognia, Jean, Bonomo, Robert A., Booth, Sarah L., Bosaeus, Ingvar G., Brenner, David J., Bridges, S. Louis, Jr., Brochard, Laurent, Brodsky, Robert A., Brook, Itzhak, Brown, Jennifer R., Brunetti, Enrico, Bryant, Amy E., Budge, Philip J., Buffet, Pierre A., Bushinsky, David A., Bykerk, Vivian P., Calabresi, Peter A., Calello, Diane P., Calfee, David P., Callahan, S. Todd, Camilleri, Michael, Canoso, Juan J., Cappellini, Maria Domenica, Carabello, Blase A., Carucci, Laura R., Castells, Mariana, Catherino, William H., Cederholm, Tommy E., Chalasani, Naga P., Chambers, Henry F., Chang, Larry W., Chang, Lin, Chao, Nelson J., Chatterjee, Mitali, Chaturvedi, Seemant, Chen, Lin H., Chen, Sharon C-A, Chon, Susan Y., Christiani, David C., Chu, Edward, Cieslak, Theodore J., Cioffi, George A., Clancy, Carolyn M., Clauss, Heather, Clauw, Daniel J., Clemmons, David R., Coffman, Thomas M., Cohen, David, Cohen, Jeffrey, Cohen, Myron S., Cohen, Steven P., Connors, Joseph M., Cook, Deborah J., Cook, Lucy B.M., Cooney, Kathleen A., Craigen, William J., Crandall, Jill P., Croft, Simon L., Crow, Mary K., Crump, John A., Cudkowicz, Merit E., Cunningham-Rundles, Charlotte, Dahir, Kathryn M., Damon, Inger K., Daras, Michael, Dart, Richard C., Davidson, Nancy E., Deane, Kevin D., DeAngelis, Lisa M., DeCamp, Malcolm M., DeLoughery, Thomas G., del Rio, Carlos, De Luca, Gabriele C., Denning, David W., Deuster, Patricia A., DeZern, Amy E., Dhatariya, Ketan K., Diasio, Robert B., Diemert, David J., Digre, Kathleen B., Dilsizian, Vasken, Dionne, Jodie A., Di Paola, Jorge, Dispenzieri, Angela, Dogra, Sunil, Doroshow, James H., Douglas, John M., Jr., Drazen, Jeffrey M., Drekonja, Dimitri, Dubberke, Erik R., DuBeau, Catherine E., Dumler, J. Stephen, Duvic, Madeleine, Ebi, Kristie, Edwards, Kathryn M., Edwards, N. Lawrence, Eikelboom, John W., Einhorn, Lawrence H., Elliott, Perry M., Emanuel, Ezekiel J., Falagas, Matthew E., Falk, Gary W., Fang, James C., Farley, Monica M., Feder, Gene, Feller-Kopman, David J., File, Thomas McDonald, Jr., Fishman, Glenn I., Flack, John M., Fleckenstein, James M., Fleisher, Lee A., Flint, Paul W., Fogel, Evan L., Fontana, Robert J., Forsmark, Chris E., Fournier, Pierre-Edouard, Fowler, Vance G., Jr., Franco, Manuel A., Fraser, Victoria J., Freeman, Roy, Freund, Karen M., Froberg, Blake A., Gallagher, Patrick G., Gandhi, Monica, Gandhi, Rajesh T., Ganz, Leonard, Garan, Hasan, Garcia-Tsao, Guadalupe, Geisler, William M., Gelfand, Joel M., George, Tony P., Gepstein, Lior, Gertz, Morie A., Ghanem, Khalil G., Gharavi, Ali G., Ghossein, Cybele, Gill, Christopher J., Ginsburg, Geoffrey S., Glesby, Marshall J., Gnann, John W., Jr., Goldman, David L., Goldman, Lee, Goldstein, Larry B., Gordon, Anthony C., Gotlib, Jason, Gotuzzo, Eduardo, Grasemann, Hartmut, Green-McKenzie, Judith, Greenberg, Harry B., Greenberg, Steven A., Greer, David M., Greysen, S. Ryan, Griffin, Marie R., Griggs, Robert C., Grossman, Daniel, Guay-Woodford, Lisa M., Gulick, Roy M., Haake, David A., Hagman, Melissa M., Hagspiel, Klaus D., Harris, Raymond C., Havers, Fiona P., Heath, Elisabeth I., Hecht, Frederick M., Hensrud, Donald D., Hess, Jeremy, Hewlett, Erik L., Hift, Richard J., Hill, David R., Hill, Nicholas S., Hillyer, Christopher D., Hirsch, Hans H., Hoeper, Marius M., Hoit, Brian D., Holers, V. Michael, Holland, Steven M., Hollenberg, Anthony N., Hollenberg, Steven M., Howard, Jo, Hunter, David J., Hussain, Khalid, Iannuzzi, Michael C., Inman, Robert D., Inouye, Sharon K., Ison, Michael G., Jen, Joanna C., Jensen, Dennis M., Jensen, Michael D., Jensen, Robert T., Johnston, S. Claiborne, Jones, Robin L., Jordan, Richard C., Kahi, Charles J., Kaiser, Laurent, Kaminski, Henry J., Kamya, Moses R., Kao, Louise W., Kaplan, Steven A., Kastner, Daniel L., Katzka, David A., Katzman, Debra K., Kaushansky, Kenneth, Kaye, Keith S., Keating, Armand, Kelley, Robin K., Kennedy, Richard B., Khuri, Fadlo R., Kim, Rose, Kirchhoff, Louis V., Kirking, Hannah, Kirtane, Ajay J., Kishnani, Priya S., Klausner, Jeffrey D., Klion, Amy D., Klompas, Michael, Knopman, David S., Ko, Christine J., Kodali, Susheel, Kontoyiannis, Dimitrios P., Koppel, Barbara S., Korenblat, Kevin M., Korf, Bruce R., Kortepeter, Mark G., Koshy, Anita A., Kottilil, Shyamasundaran, Kovacs, Joseph A., Kovacs, Thomas O., Kowdley, Kris V., Kraft, Monica, Kramer, Christopher M., Krasnewich, Donna M., Kraus, William E., Krause, Peter J., Kroger, Andrew T., Kroshinsky, Daniela, Kuemmerle, John F., Kuipers, Ernst J., Kutner, Jean S., Laheru, Daniel, Lampert, Rachel, Landefeld, C. Seth, Landovitz, Raphael J., Landry, Donald W., Lange, Richard A., Lee, Hochang B., Lee, Nelson, Levey, Andrew S., Levine, Stephanie M., Lichtenstein, Gary R., Liebmann, Jeffrey M., Liebschutz, Jane M., Lim, Henry W., Lima, Aldo A.M., Limaye, Ajit P., Limdi, Nita A., Link, Mark S., Liu, Catherine, Lloyd-Jones, Donald M., Lopez, Fred A., Louie, Arnold, Lyness, Jeffrey M., MacKenzie, C. Ronald, MacLennan, Calman A., MacMillan, Harriet L., Madoff, Robert D., Maher, Jacquelyn, Maier, Lisa A., Maldarelli, Frank, Malhotra, Atul, Manary, Mark J., Marcos, Luis A., Marelli, Ariane J., Marks, Andrew R., Marschall, Jonas, Martin, Paul, Martinez, Fernando J., Mason, Joel B., Masur, Henry, Mathers, Amy J., Matthay, Michael A., McCool, F. Dennis, McInnes, Iain B., McLaughlin, Vallerie, McMichael, Amy, McMurray, John J.V., McQuaid, Kenneth R., Mead, Paul S., Means, Robert T., Jr., Melia, Michael T., Mellinghoff, Ingo K., Melton, Genevieve B., Merrick, Samuel T., Miceli, Marisa H., Michel, Marc, Mokdad, Ali H., Moy, Ernest, Mukherjee, Debabrata, Murr, Andrew H., Myerburg, Robert J., Nadeau, Kari C., Nath, Avindra, Neal-Perry, Genevieve, Neilson, Eric G., Nelson, Christina A., Nelson, David B., Nelson, Lewis S., Nestler, Eric J., Neuzil, Kathleen M., Nieman, Lynnette K., Niven, Alexander S., O’Connor, Christopher M., O’Connor, Francis G., O’Connor, Patrick G., O’Donnell, Anne E., O’Donnell, James S., Oh, Jae K., Okun, Michael S., O’Leary, Sean T., Olgin, Jeffrey E., Olivier, Kenneth N., Olivotto, Iacopo, Olsen, Nancy J., Orenstein, Walter A., Ortel, Thomas L., O’Shea, John J., Osmon, Douglas R., Ostrem, Jill L., Ostrosky-Zeichner, Luis, Otto, Catherine M., Ottolini, Martin G., Ovsyannikova, Inna G., Pappas, Peter G., Park, Ben Ho, Patel, Robin, Patterson, Thomas F., Pawlotsky, Jean-Michel, Payne, Thomas H., Pearce, Elizabeth N., Pearson, Richard D., Perl, Trish M., Petersen, Brett W., Petri, William A., Jr., Pfeffer, Marc A., Philips, Jennifer A., Pisetsky, David S., Pletcher, Steven D., Plumb, Ian D., Poland, Gregory A., Powell, Frank, Pyeritz, Reed E., Quinn, Thomas C., Racaniello, Vincent, Radhakrishnan, Jai, Radich, Jerald, Rafailidis, Petros I., Raghu, Ganesh, Ragni, Margaret V., Rahman, Proton, Rajkumar, S. Vincent, Ralston, Stuart H., Raoult, Didier, Reboli, Annette C., Reddy, K. Rajender, Redelmeier, Donald A., Redlich, Carrie A., Reilly, John, Reller, Megan E., Reno, Hilary E.L., Resnick, Neil M., Rice, Louis B., Roach, E. Steve, Robinson, Jennifer G., Rogatsky, Inez, Rogers, Joseph G., Rolain, Jean-Marc, Rollins, Barrett J., Romero, José R., Rosen, Jennifer B., Rosenthal, Philip J., Russell, James A., Rustgi, Anil K., Safer, Joshua D., Saini, Sarbjit S., Salmon, Jane E., Salvana, Edsel Maurice T., Santoro, Nanette, Santucci, Peter A., Sarnak, Mark J., Savage, Kerry J., Savard, Patrice, Sawka, Michael N., Scanlon, Paul D., Schafer, Andrew I., Schiff, Manuel, Schilsky, Michael L., Schneider, Thomas Rudolf, Schooley, Robert T., Schriger, David L., Schuchter, Lynn M., Schwartz, Lawrence B., Seas, Carlos, Seifert, Steven A., Seifter, Julian Lawrence, Selcen, Duygu, Selim, Magdy, Semrad, Carol E., Sepulveda, Jorge, Shaw, Pamela J., Shaz, Beth H., Sheridan, Robert L., Sherman, Stuart, Shojania, Kaveh G., Shopsin, Bo, Shy, Michael E., Sidransky, Ellen, Sifri, Costi D., Siliciano, Robert F., Simel, David L., Skorecki, Karl, Slawski, Barbara A., Slutsky, Arthur S., Smetana, Gerald W., Smith, A. Gordon, Smith, Stephen R., Southwick, Frederick S., Spiegel, Allen M., Spiera, Robert, Spinola, Stanley M., Spong, Catherine Y., Stabler, Sally P., Stark, Paul, Clair, E. William St., Steiner, Theodore S., Stephens, David S., Stevens, David A., Stevens, Dennis L., Stokes, M. Barry, Stoller, James K., Stone, John H., Stone, Richard M., Su, Edwin P., Swerdloff, Ronald S., Swygard, Heidi, Sykes, Megan, Talbot, H. Keipp, Tamimi, Rulla M., Tanofsky-Kraff, Marian, Tarlo, Susan M., Taylor, Stephanie N., Teirstein, Paul S., Telford, Sam R., III, Thakker, Rajesh V., Therrien, Judith, Thompson, George R., III, Tormoehlen, Laura, Tosti, Antonella, Trehan, Indi, Umpierrez, Guillermo E., Valeri, Anthony Michael, Varga, John, Vaughn, Bradley V., Venook, Alan P., Verbalis, Joseph G., Vose, Julie M., Wachter, Robert M., Walsh, B. Timothy, Walsh, Edward E., Walsh, Thomas J., Walston, Jeremy D., Walter, Roland B., Wang, Christina, Wang, Kenneth K., Ware, Lorraine B., Warren, Cirle A., Watkins, Paul B., Weber, Thomas J., Weimer, Louis H., Weinberg, Geoffrey A., Weinstein, Robert S., Weiss, Roger D., Weiss, Roy E., Weitz, Jeffrey I., Welt, Frederick G.P., Wenzel, Richard P., Werth, Victoria P., West, Sterling G., White, A. Clinton, Jr., White, Christopher J., White, Julian, White, Perrin C., Whitley, Richard J., Whyte, Michael P., Wiebe, Samuel, Wiener-Kronish, Jeanine P., Wilber, David J., Wilcox, Mark H., Winikoff, Beverly, Winter, Jane N., Wittink, Marsha N., Wolff, Tracy A., Wolin, Edward M., Wormser, Gary P., Yancy, Clyde W., Young, Neal S., Young, Vincent B., Young, William F., Jr., Yu, Alan S.L., Zimetbaum, Peter, and Zucker, Jane R.

Published
2025
Full Text
View/download PDF

24. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency

Author

Morris, Andrew A. M., Kožich, Viktor, Santra, Saikat, Andria, Generoso, Ben-Omran, Tawfeg I. M., Chakrapani, Anupam B., Crushell, Ellen, Henderson, Mick J., Hochuli, Michel, Huemer, Martina, Janssen, Miriam C. H., Maillot, Francois, Mayne, Philip D., McNulty, Jenny, Morrison, Tara M., Ogier, Helene, O’Sullivan, Siobhan, Pavlíková, Markéta, de Almeida, Isabel Tavares, Terry, Allyson, Yap, Sufin, Blom, Henk J., and Chapman, Kimberly A.

Published
2017
Full Text
View/download PDF

37. Postauthorization safety study of betaine anhydrous

Author

Mütze, Ulrike, Gleich, Florian, Garbade, Sven F., Plisson, Céline, Aldámiz-Echevarría, Luis, Arrieta, Francisco, Ballhausen, Diana, Zielonka, Matthias, Petković Ramadža, Danijela, Baumgartner, Matthias R., Cano, Aline, García Jiménez, María Concepción, Dionisi-Vici, Carlo, Ješina, Pavel, Blom, Henk J., Couce, Maria Luz, Meavilla Olivas, Silvia, Mention, Karine, Mochel, Fanny, Morris, Andrew A.M., Mundy, Helen, Redonnet-Vernhet, Isabelle, Santra, Saikat, Schiff, Manuel, Servais, Aude, Vitoria, Isidro, Huemer, Martina, Kožich, Viktor, Kölker, Stefan, Mütze, Ulrike, Gleich, Florian, Garbade, Sven F., Plisson, Céline, Aldámiz-Echevarría, Luis, Arrieta, Francisco, Ballhausen, Diana, Zielonka, Matthias, Petković Ramadža, Danijela, Baumgartner, Matthias R., Cano, Aline, García Jiménez, María Concepción, Dionisi-Vici, Carlo, Ješina, Pavel, Blom, Henk J., Couce, Maria Luz, Meavilla Olivas, Silvia, Mention, Karine, Mochel, Fanny, Morris, Andrew A.M., Mundy, Helen, Redonnet-Vernhet, Isabelle, Santra, Saikat, Schiff, Manuel, Servais, Aude, Vitoria, Isidro, Huemer, Martina, Kožich, Viktor, and Kölker, Stefan

Published
2022

38. Postauthorization safety study of betaine anhydrous

Author

Mütze, Ulrike; https://orcid.org/0000-0002-4251-7257, Gleich, Florian; https://orcid.org/0000-0001-7397-5640, Garbade, Sven F; https://orcid.org/0000-0002-7420-4757, Plisson, Céline, Baumgartner, Matthias R; https://orcid.org/0000-0002-9270-0826, Huemer, Martina; https://orcid.org/0000-0002-0590-678X, Aldámiz‐Echevarría, Luis; https://orcid.org/0000-0003-0687-6604, Arrieta, Francisco, Ballhausen, Diana; https://orcid.org/0000-0003-2940-3439, Zielonka, Matthias; https://orcid.org/0000-0001-9653-2914, Petković Ramadža, Danijela, Cano, Aline, García Jiménez, María Concepción; https://orcid.org/0000-0002-5563-3177, Dionisi‐Vici, Carlo; https://orcid.org/0000-0002-0007-3379, Ješina, Pavel, Blom, Henk J; https://orcid.org/0000-0001-5202-9241, Couce, Maria Luz, Meavilla Olivas, Silvia, Mention, Karine, Mochel, Fanny, Morris, Andrew A M, Mundy, Helen, Redonnet‐Vernhet, Isabelle, Santra, Saikat, Schiff, Manuel, Servais, Aude; https://orcid.org/0000-0002-8165-8212, Vitoria, Isidro, Kožich, Viktor; https://orcid.org/0000-0001-5820-5277, Kölker, Stefan; https://orcid.org/0000-0001-5188-9477, Mütze, Ulrike; https://orcid.org/0000-0002-4251-7257, Gleich, Florian; https://orcid.org/0000-0001-7397-5640, Garbade, Sven F; https://orcid.org/0000-0002-7420-4757, Plisson, Céline, Baumgartner, Matthias R; https://orcid.org/0000-0002-9270-0826, Huemer, Martina; https://orcid.org/0000-0002-0590-678X, Aldámiz‐Echevarría, Luis; https://orcid.org/0000-0003-0687-6604, Arrieta, Francisco, Ballhausen, Diana; https://orcid.org/0000-0003-2940-3439, Zielonka, Matthias; https://orcid.org/0000-0001-9653-2914, Petković Ramadža, Danijela, Cano, Aline, García Jiménez, María Concepción; https://orcid.org/0000-0002-5563-3177, Dionisi‐Vici, Carlo; https://orcid.org/0000-0002-0007-3379, Ješina, Pavel, Blom, Henk J; https://orcid.org/0000-0001-5202-9241, Couce, Maria Luz, Meavilla Olivas, Silvia, Mention, Karine, Mochel, Fanny, Morris, Andrew A M, Mundy, Helen, Redonnet‐Vernhet, Isabelle, Santra, Saikat, Schiff, Manuel, Servais, Aude; https://orcid.org/0000-0002-8165-8212, Vitoria, Isidro, Kožich, Viktor; https://orcid.org/0000-0001-5820-5277, and Kölker, Stefan; https://orcid.org/0000-0001-5188-9477

Published
2022

39. Integration of metabolomics with genomics: Metabolic gene prioritization using metabolomics data and genomic variant (CADD) scores

Author

Bongaerts, Michiel (author), Bonte, Ramon (author), Demirdas, Serwet (author), Huidekoper, Hidde H. (author), Langendonk, Janneke (author), Wilke, Martina (author), de Valk, Walter (author), Blom, Henk J. (author), Reinders, M.J.T. (author), Ruijter, George J.G. (author), Bongaerts, Michiel (author), Bonte, Ramon (author), Demirdas, Serwet (author), Huidekoper, Hidde H. (author), Langendonk, Janneke (author), Wilke, Martina (author), de Valk, Walter (author), Blom, Henk J. (author), Reinders, M.J.T. (author), and Ruijter, George J.G. (author)

Abstract

The integration of metabolomics data with sequencing data is a key step towards improving the diagnostic process for finding the disease-causing genetic variant(s) in patients suspected of having an inborn error of metabolism (IEM). The measured metabolite levels could provide additional phenotypical evidence to elucidate the degree of pathogenicity for variants found in genes associated with metabolic processes. We present a computational approach, called Reafect, that calculates for each reaction in a metabolic pathway a score indicating whether that reaction is deficient or not. When calculating this score, Reafect takes multiple factors into account: the magnitude and sign of alterations in the metabolite levels, the reaction distances between metabolites and reactions in the pathway, and the biochemical directionality of the reactions. We applied Reafect to untargeted metabolomics data of 72 patient samples with a known IEM and found that in 81% of the cases the correct deficient enzyme was ranked within the top 5% of all considered enzyme deficiencies. Next, we integrated Reafect with Combined Annotation Dependent Depletion (CADD) scores (a measure for gene variant deleteriousness) and ranked the metabolic genes of 27 IEM patients. We observed that this integrated approach significantly improved the prioritization of the genes containing the disease-causing variant when compared with the two approaches individually. For 15/27 IEM patients the correct affected gene was ranked within the top 0.25% of the set of potentially affected genes. Together, our findings suggest that metabolomics data improves the identification of affected genes in patients suffering from IEM., Pattern Recognition and Bioinformatics

Published
2022
Full Text
View/download PDF

40. Integration of metabolomics with genomics:Metabolic gene prioritization using metabolomics data and genomic variant (CADD) scores

Author

Bongaerts, Michiel, Bonte, Ramon, Demirdas, Serwet, Huidekoper, Hidde H., Langendonk, Janneke, Wilke, Martina, de Valk, Walter, Blom, Henk J., Reinders, Marcel J.T., Ruijter, George J.G., Bongaerts, Michiel, Bonte, Ramon, Demirdas, Serwet, Huidekoper, Hidde H., Langendonk, Janneke, Wilke, Martina, de Valk, Walter, Blom, Henk J., Reinders, Marcel J.T., and Ruijter, George J.G.

Abstract

The integration of metabolomics data with sequencing data is a key step towards improving the diagnostic process for finding the disease-causing genetic variant(s) in patients suspected of having an inborn error of metabolism (IEM). The measured metabolite levels could provide additional phenotypical evidence to elucidate the degree of pathogenicity for variants found in genes associated with metabolic processes. We present a computational approach, called Reafect, that calculates for each reaction in a metabolic pathway a score indicating whether that reaction is deficient or not. When calculating this score, Reafect takes multiple factors into account: the magnitude and sign of alterations in the metabolite levels, the reaction distances between metabolites and reactions in the pathway, and the biochemical directionality of the reactions. We applied Reafect to untargeted metabolomics data of 72 patient samples with a known IEM and found that in 81% of the cases the correct deficient enzyme was ranked within the top 5% of all considered enzyme deficiencies. Next, we integrated Reafect with Combined Annotation Dependent Depletion (CADD) scores (a measure for gene variant deleteriousness) and ranked the metabolic genes of 27 IEM patients. We observed that this integrated approach significantly improved the prioritization of the genes containing the disease-causing variant when compared with the two approaches individually. For 15/27 IEM patients the correct affected gene was ranked within the top 0.25% of the set of potentially affected genes. Together, our findings suggest that metabolomics data improves the identification of affected genes in patients suffering from IEM.

Published
2022

42. Postauthorization safety study of betaine anhydrous

Author

Mütze, Ulrike, primary, Gleich, Florian, additional, Garbade, Sven F., additional, Plisson, Céline, additional, Aldámiz‐Echevarría, Luis, additional, Arrieta, Francisco, additional, Ballhausen, Diana, additional, Zielonka, Matthias, additional, Petković Ramadža, Danijela, additional, Baumgartner, Matthias R., additional, Cano, Aline, additional, García Jiménez, María Concepción, additional, Dionisi‐Vici, Carlo, additional, Ješina, Pavel, additional, Blom, Henk J., additional, Couce, Maria Luz, additional, Meavilla Olivas, Silvia, additional, Mention, Karine, additional, Mochel, Fanny, additional, Morris, Andrew A. M., additional, Mundy, Helen, additional, Redonnet‐Vernhet, Isabelle, additional, Santra, Saikat, additional, Schiff, Manuel, additional, Servais, Aude, additional, Vitoria, Isidro, additional, Huemer, Martina, additional, Kožich, Viktor, additional, and Kölker, Stefan, additional

Published
2022
Full Text
View/download PDF

45. Contributors

Author

Abrams, Charles S., Adler, Ronald S., Agarwal, Anupam, Akin, Cem, Aksamit, Allen J., Jr., Al-Awqati, Qais, Allen, Upton D., Allos, Ban Mishu, Angus, Derek C., Appelbaum, Frederick R., Armitage, James O., Armstrong, April W., Armstrong, Deborah K., Arnaout, M. Amin, Arnold, Robert M., Aronson, Louise, Atkinson, John P., Attia, Evelyn, Auerbach, Andrew D., Ayanian, John Z., Baddour, Larry M., Baden, Lindsey R., Bailey, Thomas C., Bain, Barbara J., Bajorin, Dean F., Baloh, Robert W., Bangham, Charles R.M., Barasch, Jonathan, Barrett, Bruce, Bartholomew, John R., Bartleson, J.D., Barton, Mary B., Basner, Robert C., Bass, Adam J., Bass, Anne R., Bauman, Julie E., Bausch, Daniel G., Bayer, Arnold S., Bazarian, Jeffrey J., Bearman, Gonzalo M., Becker, Richard C., Beckham, J. David, Beckman, Joshua A., Beigel, John H., Bel, Elisabeth H., Belda, Walter, Jr., Benarroch, Eduardo E., Berger, Joseph R., Berliner, Nancy, Bernat, James L., Bessesen, Daniel H., Bibbins-Domingo, Kirsten, Biesecker, Leslie G., Biundo, Joseph J., Blankson, Joel N., Bloch, Karen C., Blom, Henk J., Boden, William E., Boivin, Guy, Bolognia, Jean, Bonomo, Robert A., Booth, Sarah L., Bosaeus, Ingvar G., Brenner, David J., Bridges, S. Louis, Jr., Brochard, Laurent, Brodsky, Robert A., Brook, Itzhak, Brown, Jennifer R., Brunetti, Enrico, Bryant, Amy E., Budge, Philip J., Buffet, Pierre A., Bushinsky, David A., Bykerk, Vivian P., Calabresi, Peter A., Calello, Diane P., Calfee, David P., Callahan, S. Todd, Camilleri, Michael, Canoso, Juan J., Cappellini, Maria Domenica, Carabello, Blase A., Carucci, Laura R., Castells, Mariana, Catherino, William H., Cederholm, Tommy E., Chalasani, Naga P., Chambers, Henry F., Chang, Larry W., Chang, Lin, Chao, Nelson J., Chatterjee, Mitali, Chaturvedi, Seemant, Chen, Lin H., C-A Chen, Sharon, Chon, Susan Y., Christiani, David C., Chu, Edward, Cieslak, Theodore J., Cioffi, George A., Clancy, Carolyn M., Clauss, Heather, Clauw, Daniel J., Clemmons, David R., Coffman, Thomas M., Cohen, David, Cohen, Jeffrey, Cohen, Myron S., Cohen, Steven P., Connors, Joseph M., Cook, Deborah J., Cook, Lucy B.M., Cooney, Kathleen A., Craigen, William J., Crandall, Jill P., Croft, Simon L., Crow, Mary K., Crump, John A., Cudkowicz, Merit E., Cunningham-Rundles, Charlotte, Dahir, Kathryn M., Damon, Inger K., Daras, Michael, Dart, Richard C., Davidson, Nancy E., Deane, Kevin D., DeAngelis, Lisa M., DeCamp, Malcolm M., DeLoughery, Thomas G., Rio, Carlos del, De Luca, Gabriele C., Denning, David W., Deuster, Patricia A., DeZern, Amy E., Dhatariya, Ketan K., Diasio, Robert B., Diemert, David J., Digre, Kathleen B., Dilsizian, Vasken, Dionne, Jodie A., Di Paola, Jorge, Dispenzieri, Angela, Dogra, Sunil, Doroshow, James H., Douglas, John M., Jr., Drazen, Jeffrey M., Drekonja, Dimitri, Dubberke, Erik R., DuBeau, Catherine E., Dumler, J. Stephen, Duvic, Madeleine, Ebi, Kristie, Edwards, Kathryn M., Edwards, N. Lawrence, Eikelboom, John W., Einhorn, Lawrence H., Elliott, Perry M., Emanuel, Ezekiel J., Falagas, Matthew E., Falk, Gary W., Fang, James C., Farley, Monica M., Feder, Gene, Feller-Kopman, David J., McDonald File, Thomas, Jr., Fishman, Glenn I., Flack, John M., Fleckenstein, James M., Fleisher, Lee A., Flint, Paul W., Fogel, Evan L., Fontana, Robert J., Forsmark, Chris E., Fournier, Pierre-Edouard, Fowler, Vance G., Jr., Franco, Manuel A., Fraser, Victoria J., Freeman, Roy, Freund, Karen M., Froberg, Blake A., Gallagher, Patrick G., Gandhi, Monica, Gandhi, Rajesh T., Ganz, Leonard, Garan, Hasan, Garcia-Tsao, Guadalupe, Geisler, William M., Gelfand, Joel M., George, Tony P., Gepstein, Lior, Gertz, Morie A., Ghanem, Khalil G., Gharavi, Ali G., Ghossein, Cybele, Gill, Christopher J., Ginsburg, Geoffrey S., Glesby, Marshall J., Gnann, John W., Jr., Goldman, David L., Goldman, Lee, Goldstein, Larry B., Gordon, Anthony C., Gotlib, Jason, Gotuzzo, Eduardo, Grasemann, Hartmut, Green-McKenzie, Judith, Greenberg, Harry B., Greenberg, Steven A., Greer, David M., Greysen, S. Ryan, Griffin, Marie R., Griggs, Robert C., Grossman, Daniel, Guay-Woodford, Lisa M., Gulick, Roy M., Haake, David A., Hagman, Melissa M., Hagspiel, Klaus D., Harris, Raymond C., Havers, Fiona P., Heath, Elisabeth I., Hecht, Frederick M., Hensrud, Donald D., Hess, Jeremy, Hewlett, Erik L., Hift, Richard J., Hill, David R., Hill, Nicholas S., Hillyer, Christopher D., Hirsch, Hans H., Hoeper, Marius M., Hoit, Brian D., Holers, V. Michael, Holland, Steven M., Hollenberg, Anthony N., Hollenberg, Steven M., Howard, Jo, Hunter, David J., Hussain, Khalid, Iannuzzi, Michael C., Inman, Robert D., Inouye, Sharon K., Ison, Michael G., Jen, Joanna C., Jensen, Dennis M., Jensen, Michael D., Jensen, Robert T., Johnston, S. Claiborne, Jones, Robin L., Jordan, Richard C., Kahi, Charles J., Kaiser, Laurent, Kaminski, Henry J., Kamya, Moses R., Kao, Louise W., Kaplan, Steven A., Kastner, Daniel L., Katzka, David A., Katzman, Debra K., Kaushansky, Kenneth, Kaye, Keith S., Keating, Armand, Kelley, Robin K., Kennedy, Richard B., Khuri, Fadlo R., Kim, Rose, Kirchhoff, Louis V., Kirking, Hannah, Kirtane, Ajay J., Kishnani, Priya S., Klausner, Jeffrey D., Klion, Amy D., Klompas, Michael, Knopman, David S., Ko, Christine J., Kodali, Susheel, Kontoyiannis, Dimitrios P., Koppel, Barbara S., Korenblat, Kevin M., Korf, Bruce R., Kortepeter, Mark G., Koshy, Anita A., Kottilil, Shyamasundaran, Kovacs, Joseph A., Kovacs, Thomas O., Kowdley, Kris V., Kraft, Monica, Kramer, Christopher M., Krasnewich, Donna M., Kraus, William E., Krause, Peter J., Kroger, Andrew T., Kroshinsky, Daniela, Kuemmerle, John F., Kuipers, Ernst J., Kutner, Jean S., Laheru, Daniel, Lampert, Rachel, Landefeld, C. Seth, Landovitz, Raphael J., Landry, Donald W., Lange, Richard A., Lee, Hochang B., Lee, Nelson, Levey, Andrew S., Levine, Stephanie M., Lichtenstein, Gary R., Liebmann, Jeffrey M., Liebschutz, Jane M., Lim, Henry W., Lima, Aldo A.M., Limaye, Ajit P., Limdi, Nita A., Link, Mark S., Liu, Catherine, Lloyd-Jones, Donald M., Lopez, Fred A., Louie, Arnold, Lyness, Jeffrey M., MacKenzie, C. Ronald, MacLennan, Calman A., MacMillan, Harriet L., Madoff, Robert D., Maher, Jacquelyn, Maier, Lisa A., Maldarelli, Frank, Malhotra, Atul, Manary, Mark J., Marcos, Luis A., Marelli, Ariane J., Marks, Andrew R., Marschall, Jonas, Martin, Paul, Martinez, Fernando J., Mason, Joel B., Masur, Henry, Mathers, Amy J., Matthay, Michael A., McCool, F. Dennis, McInnes, Iain B., McLaughlin, Vallerie, McMichael, Amy, McMurray, John J.V., McQuaid, Kenneth R., Mead, Paul S., Means, Robert T., Jr., Melia, Michael T., Mellinghoff, Ingo K., Melton, Genevieve B., Merrick, Samuel T., Miceli, Marisa H., Michel, Marc, Mokdad, Ali H., Moy, Ernest, Mukherjee, Debabrata, Murr, Andrew H., Myerburg, Robert J., Nadeau, Kari C., Nath, Avindra, Neal-Perry, Genevieve, Neilson, Eric G., Nelson, Christina A., Nelson, David B., Nelson, Lewis S., Nestler, Eric J., Neuzil, Kathleen M., Nieman, Lynnette K., Niven, Alexander S., O’Connor, Christopher M., O’Connor, Francis G., O’Connor, Patrick G., O’Donnell, Anne E., O’Donnell, James S., Oh, Jae K., Okun, Michael S., O’Leary, Sean T., Olgin, Jeffrey E., Olivier, Kenneth N., Olivotto, Iacopo, Olsen, Nancy J., Orenstein, Walter A., Ortel, Thomas L., O’Shea, John J., Osmon, Douglas R., Ostrem, Jill L., Ostrosky-Zeichner, Luis, Otto, Catherine M., Ottolini, Martin G., Ovsyannikova, Inna G., Pappas, Peter G., Park, Ben Ho, Patel, Robin, Patterson, Thomas F., Pawlotsky, Jean-Michel, Payne, Thomas H., Pearce, Elizabeth N., Pearson, Richard D., Perl, Trish M., Petersen, Brett W., Petri, William A., Jr., Pfeffer, Marc A., Philips, Jennifer A., Pisetsky, David S., Pletcher, Steven D., Plumb, Ian D., Poland, Gregory A., Powell, Frank, Pyeritz, Reed E., Quinn, Thomas C., Racaniello, Vincent, Radhakrishnan, Jai, Radich, Jerald, Rafailidis, Petros I., Raghu, Ganesh, Ragni, Margaret V., Rahman, Proton, Rajkumar, S. Vincent, Ralston, Stuart H., Raoult, Didier, Reboli, Annette C., Reddy, K. Rajender, Redelmeier, Donald A., Redlich, Carrie A., Reilly, John, Reller, Megan E., Reno, Hilary E.L., Resnick, Neil M., Rice, Louis B., Roach, E. Steve, Robinson, Jennifer G., Rogatsky, Inez, Rogers, Joseph G., Rolain, Jean-Marc, Rollins, Barrett J., Romero, José R., Rosen, Jennifer B., Rosenthal, Philip J., Russell, James A., Rustgi, Anil K., Safer, Joshua D., Saini, Sarbjit S., Salmon, Jane E., Salvana, Edsel Maurice T., Santoro, Nanette, Santucci, Peter A., Sarnak, Mark J., Savage, Kerry J., Savard, Patrice, Sawka, Michael N., Scanlon, Paul D., Schafer, Andrew I., Schiff, Manuel, Schilsky, Michael L., Schneider, Thomas Rudolf, Schooley, Robert T., Schriger, David L., Schuchter, Lynn M., Schwartz, Lawrence B., Seas, Carlos, Seifert, Steven A., Seifter, Julian Lawrence, Selcen, Duygu, Selim, Magdy, Semrad, Carol E., Sepulveda, Jorge, Shaw, Pamela J., Shaz, Beth H., Sheridan, Robert L., Sherman, Stuart, Shojania, Kaveh G., Shopsin, Bo, Shy, Michael E., Sidransky, Ellen, Sifri, Costi D., Siliciano, Robert F., Simel, David L., Skorecki, Karl, Slawski, Barbara A., Slutsky, Arthur S., Smetana, Gerald W., Smith, A. Gordon, Smith, Stephen R., Southwick, Frederick S., Spiegel, Allen M., Spiera, Robert, Spinola, Stanley M., Spong, Catherine Y., Stabler, Sally P., Stark, Paul, St. Clair, E. William, Steiner, Theodore S., Stephens, David S., Stevens, David A., Stevens, Dennis L., Stokes, M. Barry, Stoller, James K., Stone, John H., Stone, Richard M., Su, Edwin P., Swerdloff, Ronald S., Swygard, Heidi, Sykes, Megan, Talbot, H. Keipp, Tamimi, Rulla M., Tanofsky-Kraff, Marian, Tarlo, Susan M., Taylor, Stephanie N., Teirstein, Paul S., Telford, Sam R., III, Thakker, Rajesh V., Therrien, Judith, Thompson, George R., III, Tormoehlen, Laura, Tosti, Antonella, Trehan, Indi, Umpierrez, Guillermo E., Valeri, Anthony Michael, Varga, John, Vaughn, Bradley V., Venook, Alan P., Verbalis, Joseph G., Vose, Julie M., Wachter, Robert M., Walsh, B. Timothy, Walsh, Edward E., Walsh, Thomas J., Walston, Jeremy D., Walter, Roland B., Wang, Christina, Wang, Kenneth K., Ware, Lorraine B., Warren, Cirle A., Watkins, Paul B., Weber, Thomas J., Weimer, Louis H., Weinberg, Geoffrey A., Weinstein, Robert S., Weiss, Roger D., Weiss, Roy E., Weitz, Jeffrey I., Welt, Frederick G.P., Wenzel, Richard P., Werth, Victoria P., West, Sterling G., White, A. Clinton, Jr., White, Christopher J., White, Julian, White, Perrin C., Whitley, Richard J., Whyte, Michael P., Wiebe, Samuel, Wiener-Kronish, Jeanine P., Wilber, David J., Wilcox, Mark H., Winikoff, Beverly, Winter, Jane N., Wittink, Marsha N., Wolff, Tracy A., Wolin, Edward M., Wormser, Gary P., Yancy, Clyde W., Young, Neal S., Young, Vincent B., Young, William F., Jr., Yu, Alan S.L., Zimetbaum, Peter, and Zucker, Jane R.

Published
2024
Full Text
View/download PDF

47. Homocysteine-Induced Apoptosis in Endothelial Cells Coincides With Nuclear NOX2 and Peri-nuclear NOX4 Activity

Author

Sipkens, Jessica A., Hahn, Nynke, van den Brand, Carlien S., Meischl, Christof, Cillessen, Saskia A. G. M., Smith, Desirée E. C., Juffermans, Lynda J. M., Musters, René J. P., Roos, Dirk, Jakobs, Cornelis, Blom, Henk J., Smulders, Yvo M., Krijnen, Paul A. J., Stehouwer, Coen D. A., Rauwerda, Jan A., van Hinsbergh, Victor W. M., and Niessen, Hans W. M.

Published
2013
Full Text
View/download PDF

48. Cystathionine β‐synthase deficiency in the E‐HOD registry‐part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis

Author

Kožich, Viktor, Sokolová, Jitka, Morris, Andrew A M, Pavlíková, Markéta, Gleich, Florian, Kölker, Stefan, Krijt, Jakub, Dionisi‐Vici, Carlo, Baumgartner, Matthias R, Blom, Henk J, Huemer, Martina, and University of Zurich

Subjects
2716 Genetics (clinical), 1311 Genetics, 10036 Medical Clinic, 610 Medicine & health
Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results