Genetic Mistakes: Understanding and Living with Fatty Acid Oxidation Disorders
Rosemary Forrest and Nicole Baugh
University of Arizona/HiRISE, Tucson, AZ, USA
Series: Metabolic Diseases – Laboratory and Clinical Research
BISAC: MED027000
Details
This book tackles a complex subject with both science and the heart. A diagnosis of any serious disease is life-altering and frightening. At such times, patients and their families look to their doctors for answers and treatment. Support groups help the newly diagnosed face their challenges and their experiences, removing feelings of isolation. However, when the diagnosis is a rare disorder, especially when diagnosed in an infant, none of that may follow.
Genetic Mistakes is about one class of such disorders. These metabolic mistakes strike nearly every cell in the body, reducing energy and threatening a myriad of potential problems from muscle pain and neurological issues to coma and even death. Known as FAODs, or FODs, they present complex problems with no established therapies except dietary restrictions and supplements.
Genetic Mistakes provides those affected by FAODs – including patients, parents, and primary medical personnel – with accessible, basic information. While it is not meant to take the place of medical care or medical references, it does offer both layman and primary caregivers a quick link to both current knowledge about FAODs and insight into those who must live with them.
Divided into three sections, Genetic Mistakes takes on the science and genetics of FAODs, explaining them in a plain and unemotional, yet sensitive language. The first section deals with understanding FAODs. It relies heavily on both recent and historic scientific studies and will lead the reader to see that while there is no cure, there is hope. It explains how the disorders are inherited, how they affect the body, and how patients can help themselves by understanding both the potential effects of their disorders and how their own behavior might influence it. It teases out the individual FAODs and gives the information most desired by those affected: What tests might I need? What symptoms are common? How severe is this?
The second section in Genetic Mistakes addresses the issues of learning to live with FAODs. Whether people are raising a child with one, or must cope with a later-onset FAOD themselves, these pages hold the stories, tips, and wisdom of those who have gone before. It also provides some insight into the research that may provide answers in the future.
The final section of Genetic Mistakes is meant as a springboard for readers, providing them with both the references consulted for the book as well as other useful websites, organizations, books, and more to help them understand their disorders and live confident lives. (Imprint: Nova Biomedical)
Preface
Acknowledgments
Part I. Understanding the Science and Genetics of Fatty Acid Oxidation Disorders
Chapter 1. Metabolic and Fatty Acid Oxidation Disorders (FAODs)
Chapter 2. Genetics of Fatty Acid Oxidation Disorders
Chapter 3. Sudden Infant Death Syndrome (SIDS) or “Crib Death” and the Newborn Screen (NBS)
Chapter 4. FAODs in General
Chapter 5. Disorders of Transport/Carnitine Cycle Defects
Chapter 6. Beta Oxidation (â-Oxidation) Disorders
Chapter 7. Disorders of Mitochondrial Respiratory Chain Electron Transfer and Unspecified FAODs
Part II. AN FAOD in the Family
Chapter 8. Congratulations … Oh, Wait!
Chapter 9. The Elephant in the Room
Chapter 10. The Diagnosis
Chapter 11. What Now?
Chapter 12. Finding the New Normal
Chapter 13. Educating Others
Chapter 14. Help from the Trenches
Chapter 15. Facing Family-Planning
Chapter 16. As if Things Weren’t Complicated Enough!
Chapter 17. Having a Life
Chapter 18. Hope for the Future
Part III. Resources and References
Chapter 19. General Resources and References
About the Authors
Index
“Rosemary Forrest and Nicole Baugh have used both their professional and personal experiences to write a wonderful and lay-friendly book for families living with a Fatty acid Oxidation Disorder (FOD), as well as for medical professionals that may not be familiar with these rare metabolic disorders. They give ‘direction and hope’ and understanding to families that are new to their diagnosis and treatment which helps to calm many of the fears that accompany a genetic diagnosis, especially for a newborn. Their writing and organization of the book flows in a way that decreases the complexity of technical medical terms, processes, and research and helps families understand that having an FOD is NOT a death sentence. Yet, they also share how living with these disorders can impact not only the affected child or adult, but the entire family system at home, at school/work and when hospitalized. Every chapter provides valuable information for families and professionals as they begin their journey through diagnosis, treatment, and living their lives with an FOD. Their Resource section provides informational links so families do not feel so alone and gives ways to connect with online and/or face-to-face emotional and practical Support resources, as well as links to find more medical information or possible medical support and clinical trials for new drugs. This book will give families a way to ‘wrap their heads around’ FODs without totally overwhelming them. I highly recommend this book to all affected individuals and families with FOD and for new and seasoned medical professionals.” - Deb Lee Gould, MEd, Founder/Director of the FOD (Fatty Oxidation Disorders) Family Support Group
Amendt, Brad A., Carole Greene, Larry Sweetman, John Cloherty, Vivian Shih Anne Moon, Lisa Teel, and William J. Rhead. 1987. “Short-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Clinical and Biochemical Studies in Two Patients.” The American Society for Clinical Investigation, Inc. 79:1303-1309.
Andresen, Brage Storstein, Steve F. Dobrowolski, Linda O'Reilly, Joseph Muenzer, Shawn E. McCandless, Dianne M. Frazier, Szabolcs Udvari, Peter Bross, Inga Knudsen,Rick Banas, Donald H. Chace, Paul Engel,Edwin W. Naylor, and Niels Gregersen. 2001. “Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Mutations Identified by MS/MS-Based Prospective Screening of Newborns Differ from Those Observed in Patients with Clinical Symptoms: Identification and Characterization of a New, Prevalent Mutation That Results in Mild MCAD Deficiency.” American Journal of Human Genetics. 68(6): 1408–1418. doi: 10.1086/320602.
Bastin, Jean. 2014. “Regulation of mitochondrial fatty acid β-oxidation in human: “What can we learn from inborn fatty acid b-oxidation deficiencies?” Biochimie. 96:113-20. doi:10.1016/j.biochi.2013. 05.012.
Belkadi, Aziz, Alexandre Bolze, Yuval Itan, Aurelie Cobat, Quentin B. Vincent, Alexander Antipenko, Lei Shang, Bertrand Boisson, Jean-Laurent Casanova, and Laurent Abel. 2015. “Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variant.” PNAS. 28:112-17. (Belkadi 2015) doi:10.1073/pnas.1418631112.
Besten, Gijs den, Karen van Eunen, Albert K. Groen, Koen Venema, Dirk-Jan reijngoud, and Barbara M. Bakker. 2013. “The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.”
Journal of Lipid Research. 54(9): 2325-2340. Doi: 10.1194/jlr.R036012.
Bonnefont, Jean-Paul, Fatima Djouadi, Carina Pip-Buus, Stephanie Gobin, Arnold Munnich, Jean Bastin. 2004. “Carnitinie palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects.” Molecular Aspects of Medicine. 25(5-6):495-520. doi:10.1016/j.mam.2004. 06.004.
Bouchireb, Karim, Anne-Marie Teychene, Odile Rigal, Pascale de Lonlay, Vassili Valayannopoulos, Joel Gaudeus, Nicolas Sellier, J. P. Bnnefont, Michele Brivet, Loic de Pontual. 2010. “Post-mortem MRI reveals CPT2 deficiency after sudden infant death.” European Journal of Pediatrics – Short Report. 169: 1561-1563. doi: 10.1007/s00431-010-1261-0.
Casals, N, Zammit V, Herrero L, Fadó R, Rodríguez-Rodríguez R, Serra D. 2015. “Carnitine palmitoyltransferase 1C: From cognition to cancer.” 61:134-48. doi:10.1016/j.plipres.2015.11.004.
Clemente, Florian J., Alexia Cardona, Charlotte E. Inchley, Benjamin M. Peter, Guy Jacobs, Luca Pagani, Daniel J. Lawson, Tiago Antão, Mário Vicente, Mario Mitt, Michael DeGiorgio. 2014. “A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations.” The American Journal of Human Genetics. 95(5) 6:584–589. http://doi.org/10.1016/j.ajhg.2014.09.016.
Couce, Maria Luz, Paula Sanchez-Pintos, Luisa Diogo, Elisa Leao-Teles, Esmeralda Martins, Helena Santos, Maria Amor Bueno, Carmen Delgado-Pecellin, Daisy E. Castineiras, Jose A Cocho, Judit Garcia-Villoria, Antonia Ribes, Jose M. Fraga, and Hugo Rocha. 2013. “Newborn screening for medium-chain acyle-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency.” Orphanet Journal of Rare Diseases. 10;8:102. doi:10.1186/1750-1172-8-102.
Christensen, Erik D., Justin Berger, Mouied M. Alashari, Hilary Coon Cynthia Robison, Hsu-Tso Ho, Daid R. Adams, William A. Gahl, Ken R. Smith, John m. Opitz, Dennis R. Johnson. 2016. “Sudden infant death “syndrome” Insights and future directions from a Utah population database analysis.” American Journal of Medical Genetics Part A 173, no. 1: 177-182. doi:10.1002/ajmg.a.37994.
de Sain-van der Velden,M.G., E.F. Diekman, J.J. Jans, M. van der Ham, B.H. Prinsen, G. Visser, N.M. Verhoeven-Duif. 2013. “Differences between acylcarnitine profiles in plasma and bloodspots.” Molecular Genetics and Metabolism. 110(1-2):116-21. doi: 10.1016/j.ymgme. 2013.04.008. Epub 2013 Apr 13.
Di Mauro, Salvatore and Eric Schon. 2003. “Mitochondrial Respiratory-Chain Diseases.” New England Journal of Medicine. 348:2656-2668. DOI:10.1056/NEJMra022567.
DiMauro, Salvatore and Eric A. Schon. 2003. “Mitochondrial Respiratory-Chain Diseases.” The New England Journal of Medicine 348:2656-68. doi:10.1016/j.bbadis.2008.10.015.
El-Hattab, Ayman W. 2012 (updated 2016). “Systemic Primary Carnitine Deficiency. Gene Reviews. Seattle (WA).
Ensenauer, Regina, Miao He, Jan-Marie Willard, Eric S. Goetzman, Thomas J. orydon, Brian B. Vandahl, Al-Walid Mohsen, Grazia Isaya, and Jerry Vockley. 2005. “Human Acyl-CoA Dehydrogenase-9 Plays a Novel Role in the Mitochondrial B-Oxidation of Unsaturated Fatty Acids.” The Journal of Biological Chemistry, 280(37):32309-16.
Evans, Jane A. 2015. “Old meets new: identifying founder mutations in genetic disease.” CMAJ. 187: 2 doi: 10.1503/cmaj.141509.
Ezkurdia, Iakes, David Juan, Jose Manuel Rodriguez, Adam Frankish, Mark Diekhans, Jennifer Harrow, Jesus Vazquez, Alfonso Valencia, Michael L. Tress. 2014 “Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes.” Human Molecular Genetics. 23 (22): 5866-5878. https://doi.org/10.1093/ hmg/ddu309.
Fanin,M., A Anichini, D Cassandrini, C Fiorillo, S Scapolan, C Minetti, M Cassanello, MA Donati, G Siciliano, A D’Amico, F Lilliu, C Bruno, and C Angelini. 2012. “Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT-II deficiency” Clinical Genetics. 82(3):232-9. doi: 10.1111/j.1399-0004.2011.01786.x.
Fletcher, Autumn L., Mark E. Pennesi, Cary O. Harding, Richard G. Weleber, and Melanie B. Gillinham. 2012. “Observations regarding retinopathy in mitochondrial trifunctional protein deficiencies.” Molecular Genetics and Metabolism. 106(1):18-24. doi:10.1016/ j.ymgme.2012.02.015.
Fukao, Toshiyuki. 2001. Update: 2004. “Beta-ketothiolase deficiency.” Orphanet (encyclopedia). Editor: Udu Wendel. http://www.orpha.net/ data/patho/GB/uk-T2.pdf.
Gregersen, Niels, Vibeke S. Winter, Morton J. Corydon, Thomas J. Corydon, Piero Rinaldo, Antonia Ribes, Gemma Martinez, Michael J. Bennett, Christine Vianey-Saban, Ajay Bhala, Daniel E. Hale, Willy Lehnert, Stanislav Kmoch, Manel Roig, Encamacio Riudo, Hans Eiberg, Brage S. Andresen, Peter Bross, Lars A. Bolund, and Steen Kolvraa. 1998. “Identification of four new mutations in the short-chain acyl-CoA dehydrogenase (SCAD) gene in two patients: one of the variant alleles, 511C-->T, is present at an unexpectedly high frequency in the general population, as was the case for 625G-->A, together conferring susceptibility to ethylmalonic aciduria.” Human Molecular Genetics. 7(4):619-27.
Grimm, Eleanor R. and Nanette I. Steinle. 2011. “Genetics of Eating Behavior: Established and Emerging Concepts.” Nutrition Reviews. 69(1):52-60. doi:10.1111/j.1753-4887.2010.00361.x.
Han, Jaeseok and Randal Kaufman. 2016. “The role of ER stress in lipid metabolism and lipotoxicity.” Digestive Diseases and Sciences. 44(8 Suppl):97S-102S.
Harding, Cary O. 2017. ”Fatty Acid β-Oxidation Defects.” In Metabolic Diseases, edited by E. Gilbert Barness, L.A. Barness, and P.M. Farrell, 155 – 189. IOS Press: doi:10.3233/978-1-61499718-4-155.
He, M., S. L. Rutledge, D. R. Kelly, C. A. Palmer, G. Murdoch, N. Majumder, R. D. Nicholls, Z. Pei, P. A. Watkins, and J. Vockley. 2007. “A New Genetic Disorder in Mitochondrial Fatty Acid β-Oxidation: ACAD9 Deficiency.” American Journal of Human Genetics. 81:87-103. doi:http://dx.doi.org/10.1086/519219.
Henningsson, Asa, Inger Bjorck, and Margareta Nyman. 2001. Scandinavian Journal of Nutrition. 45:165-68.
Houten, Sander M., Sara Violante, Fatima V Ventura, and Ronald J. A. Wanders. 2016. “The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders.” In Annual Review of Physiology. 78: 23-44. Originally published online as a Review in Advance on October 14, 2015: doi: 10.1146/annurev-physiol-021115-105045.
Houten, Sander M., Simone Denis, Heleen te Brinke, Aldo Jongejan, Antoine H.C. van Kampen, Edward J. Bradley, Frank Baas, Raoul C.M. Hennekam, David S. Millington, Sarah P. Young, Dianne M. Frazier, Muge Gucsavas-Calikoglu, Ronald J.A. Wanders. 2014. “Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.” Human Molecular Genetics. 23 (18): 5009-5016. doi: 10.1093/hmg/ddu218.
Innis, Sheila M. 2007. “Dietary (n-3) Fatty Acids and Brain Development.” The Journal of Nutrition. 137:855-859.
Joshi PR, Deschauer M, Zierz S. 2012. “Clinically symptomatic heterozygous carnitine palmitoyltransferase II (CPTII) deficiency.” Wien Klin Wochenschr. 124(23-24):851-4. doi: 10.1007/s00508-012-0296-9.
JP, Orlowski. 1999. “Whatever happened to Reye’s syndrome? Did it ever really exist?” Critical Care Medicine. 27(8):1582-7.
Kang, Heejung. 2014. “Exploring Therapeutic Approaches for Treatment of Medium-Chain Acyl-CoA Dehydrogenase (Mcad) Deficiency.” PhD diss., University of Pittsburg.
Lee, Jieun, Joseph Choi, Susanna Scafidi, Michael Wolfgang. 2016. “Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation.” Cell Reports. 16(1):201-12. doi: 10.1016/j.celrep. 2016.05.062.
Lovera, Cristina, Francesco Porta, Anna Caciotti, Serena Catazi, Michela Cassanello, Ubaldo Caruso, Maria Rita Gallina, amelia Morrone, and Marco Spada. 2012. “Sudden unexpected infant death (SUDI) in a newborn due to medium chain acyl CoA dehydrogenase (MCAD) deficiency with an unusual severe genotype.” Italian Journal of Pediatrics. 38:59. doi:10.1186/1824-7288-38-59.
Maher, Amy, Al-Walid Mohsen, Jerry Vockley, and Mark Tarnopolsky. 2010. “Low expression of long-chain acyl-CoA dehydrogenase in human skeletal muscle.” Molecular Genetic Metabolism. 2010. 100(2):163-7. doi: 10.1016/j.ymgme.2010.03.011.
Matern, Dietrich, and Piero Rinaldo. 2015. “Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency.” Gene Reviews. Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle, WA: University of Washington.
Mazariegos, George, Benjamin Shneider, Barbara Burton, Ira J. Fox, Nedium Hadzic, Priya Kishnani, D. Holmes Morton, Sara Mcintire, Ronald J. Sokol, Marshall Summar, Desiree White, Vincent Chavanon, Jerry Vockley. 2014. “Liver transplantation for pediatric metabolic disease.” Molecular Genetics and Metabolism, Conference Proceedings 2014. Volume 111, Issue 4: 418–427.
Moczulski, Dariusz, Iwona Majak, Dariusz Mamczur. 2009. “An Overview of B-Oxidation Disorders” Biochemical and Biophysical Research Communications 63:266-277.
Morris, A. A.M. 1999. “Mitochondrial respiratory chain disorders and the liver.” Liver. 19:357-368.
Morris, Andrew A.M and Ute Spiekerkoetter. 2012. “Disorders of Mitochondrial Fatty Acid Oxidation and Related Metabolic Pathways.” In Inborn Metabolic Diseases, 5th Edition. Edited by Jean Marie Saudubray, Georges van den Berghe, and John H. Walter. Springer-Verlag Berlin Heidelberg, Germany.
Nieland, J.D., J.G. Nieland, A.S. Mørkholt, L. Bolther, S. Nielsen. 2015. “CPT1a mutation leads the way for new medication for the treatment of multiple sclerosis.” ECTRIMS Online Library. 116347.
Olsen, RK, Cornelius N, Gregersen N. 2013. “Genetic and cellular modifiers of oxidative stress: What can we learn from fatty acid oxidation defects?” Molecular Genetics and Metabolism. 110 Suppl:531-539. DOI:10.1016/j.ymgme.2013.10.007.
Orngreen, MC, KL Madsen, N Preisler, G Andersen, J Vissing and P Laforet. 2014. “Bezafibrate in skeletal muscle fatty acid oxidation disorders: a randomized clinical trial.” Neurology. 82(7): 607–613. doi:10.1212/WNL.0000000000000118.
Orngreen, Mette C. Olpin SE, Afifi A, Clarks, Manning NJ, Bonham JR, Dalton A, Leonard JV, Land JM, Andresen BS, Morris AA, Muntoni F, Turnbull D, Pourfarzam M, Rahman S, Pollitt RJ. 2003. “Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPTII) deficiency.” Journal of Inherited Metabolic Diseases. (26)6: 543–557. (Olpin 2003, 543) doi:10.1023/A:1025947930752.
Orngreen, Mette C., Morten Duno, Rasmus Ejstrup, Ernst Christensen, Marianne Schwartz, Massimo Sacchetti, and John Vissing. 2004. “Fuel Utilization in Subjects with Carnitine Palmitoyltransferase 2 Gene Mutations.” Annals of Neurology. (57)1:60-66.
Pedersen, Christina B., Steen Kolvraa, Agnete Kolvraa, Vibeke Stenbroen, Margrethe Kjeldsen, Regina Ensenauer, Ingrid Tein, Dietrich Matern, Piero Rinaldo, Christine Vianey-Saban, Antonia Ribes, Willy Lehnert, Ernst Christensen, Thomas J. Corydon, Brage S. Andresen, Soren Vang, lars Bolund, Jerry Vockley, Peter Bross, Niels Gregersen. 2008. “The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level.”
Human Genetics. 124(1):43-56. doi:10.1007/s00439-008-0521-9.
Primassin, Sonja, Frank ter Veld, Ertan Mayatepek, and Ute Spiekerkoetter. 2008. “Carnitine Supplementation Induces Acylcarnitine Production in Tissues of Very Long-Chain Acyl-CoA Dehydrogenase-Deficient Mice, Without Replenishing Low Free Carnitine.” Pediatric Research. 63:6, 632-637.
Qu, Q., F. Zeng, X Liu, Q. J. Wang, and F. Deng. 2016. “Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer.” Cell Death and Disease. http://www.nature.com/ cddis/journal/v7/n5/pdf/cddis2016132a.pdf. doi:10.1038/cddis.2016.132.
Ramachandran, Tarakad S., 2014. “Inherited Metabolic Disorders Overview.” Neurology. http://emedicine.medscape.com/article/1183 253-overview.
Rector, R. Scott, R. Mark Payne, Jamald. A. Ibdah. 2008. “Mitochondrial trifunctional protein defects: Clinical implications and therapeutic approaches.” Advanced Drug Delivery Reviews. 60(13–14):1488–1496. doi:10.1016/j.addr.2008.04.014.
Rinaldi, C, Schmidt T, Situ AJ, Johnson JO, Lee PR, Chen K, Bott LC, Fadó R, Harmison GH, Parodi S, Grunseich C, Renvoisé B, Biesecker LG, De Michele G, Santorelli FM, Filla A, Stevanin G, Dürr A, Brice A, Casals N, Traynor BJ, Blackstone C, Ulmer TS, Fischbeck KH. 2015. “Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia.” JAMA Neurol. 72(5):561-570. doi:10.1001/jamaneurol.2014.4769.
Rinaldo, P. 1999. “Mitochondrial fatty acid oxidation disorders and cyclic vomiting syndrome.”
Rinaldo, Piero, Dietrich Matern, Michael J. Bennett. 2002. “Fatty Acid Oxidation Disorders” In Annual Review Physiology, 477-496. (Rinaldo 2002) doi: 10.1146/annurev-nutr-071812-161139.
Roe, C.R., D. S. Millington, D L. Norwood, N. Kodo, H. Sprecher, B.S. Mohammed, M. Nada, H. Schulz, and R. McVie. 1990. “2,4-Dienoyl-Coenzyme A Reductase Deficiency: A Possible New Disorder of Fatty Acid Oxidation.” Journal of Clinical Investigation. 85:1703-1707.
Schaefer, Jochen, Sandra Jakson, Franco Taroni, Peter Swift, Douglass M. Turnbull. 1997. “Characterisation of carnitine palmitoyltransferases in patients with a carnitine palmitoyltransferase deficiency: implications for diagnosis and therapy.” Journal of Neurology, Neurosurgery, and Psychiatry. 71(4): 260–264. doi:10.1212/01.wnl.0000318283.42961. e9.
Schaffer, Jean. 2016. “Lipotoxicity: Many Roads to Cell Dysfunction and Cell Death” Journal of Lipid Research. 57:1327-1328. E069880v157/ 8/1327. doi: 10.1194/jlr.E069880.
Schiff, Manuel, Birgit Haberberger, Chuanwu Xia, Al-Walid Mohsen, Eric S. Goetzman, Yudon Wang, Radha Uppala, Yuxun Zhang, AnuradhaKarunanidhi, Dolly Prabhu, Hana Alharbi, Edward V. Prochownik, Tobian Haack, Johannes Haberle, Arnold Munnich, Agnes Rotig, Robert W. Taylor, Robert D. Nicholls, Jung-Ja Kim, Holger Prokisch, and Jerry Vockley. 2015. Human Molecular Genetics. 24(11):3238-3247.
Schonfeld, Peter, and Georg Reiser. 2013. “Why does brain metabolism not favor burning of fatty acids to provide energy? – Reflections on disadvantages of the use of free fatty acids as fuel for brain.” Journal of Cerebral Blood Flow & Metabolism. 33:1493-1499. Doi:10.1038/ jcbfm.2013.128.
Se Jin, An, Sook Za Kim, Gu Hwan Kim, Han Wook Yoo, MD, and Han Hyuk Lim. 2016. “Compound heterozygous mutations of ACADS gene in newborn with short chain acyl-CoA dehydrogenase deficiency: case report and literatures review.” doi:10.3345/ kjp.2016.59.11.S45.
Serra, Paula, Mera, Maria Ida Malandrino, Joan Francesc Mir, and Laura Herrero. 2013. “Mitochondrial Fatty Acid Oxidation in Obesity.” Antioxid Redox Signal. 19(3): 269–284. doi:10.1089/ars.2012.4875.
Shekhawat, Prem S., Dietrich Matern, and Arnold W. Strauss. 2005. “Fatty acid oxidation disorders, Their Effect on Maternal Health and Neonatal Outcome: Impact of Expanded Newborn Screening on Their Diagnosis and Management” Pediatric Research, Vol. 57. No. 5, Pt 2: 78R-86R. doi:10.1203/01.PDR.0000159631.63843.3E.
Sim, Keow G., Judith Hammond, Bridget Wilcken. 2002. “Strategies for the diagnosis of mitochondrial fatty acid β-oxidation disorders.” Clinica Chimica Acta. 323:37-58.
Solis, J.O., and R. H Singh. 2002. “Management of fatty acid oxidation disorders: a survey of current treatment strategies.” Journal of American Dietetic Association. Volume 102, Issue 12:1800–1803.
Spiekerkoetter, Ute and Marinus Duran. “Mitochondrial Fatty Acid Oxidation Disorders.” In Physician’s Guide to the Diagnosis, Treatment, and Follow-up of Inherited Metabolic Disorders, edited by Thöny, B., Duran, M., Gibson, K.M., Dionisi-Vici, C. 247-264. Springer-Verlag Berlin Heidelberg.
Stanley, Charles A., Michael J. Bennett, Ertan Mayatepek. 2006. “Disorders of Mitochondrial Fatty Acid Oxidation and Related Metabolic Pathways.” In Inborn Metabolic Diseases, edited by John Fernandes, Jean-Marie Saudubray, Georges van den Berghe, John H. Walter, 175-190. Heidelberg: Springer-Verlag Berlin.
Sturm, Marga, Diran Herebian, Martina Mueller, Maurice Laryea, Ute Spiekerkoetter. 2012. PLoS One. “Functional Effects of Different Medium-Chain Acyl-CoA Dehydrogenase Genotpes and Identification of Asymptomatic Variants.” PLOS ONE 7(9):e45110. doi: 10.1371/journal.pone.0045110.
Sweetman, Lawrence, David S. Millington, Bradford L. Therrell,, Bradley Popovich,, Michael S. Watson, Marie Y. Mann, Michele A. Lloyd-Puryear, Peter C. van Dyck. 2006. “Naming and Counting Disorders (Conditions) Included in Newborn Screening Panels.” Pediatrics 117:S308-314. doi:10.1542/peds.2005-2633J.
Taggart RT, Smail D, Apolito C, Vladutiu GD. 1999. “Novel mutations associated with carnitine palmitoyltransferase II deficiency.” Human Mutation. 13(3):210-20. Doi:10.1002/(SICI)1098-1004(1999)13:3< 210::AID-HUMU5>3.0.CO;2-0.
Tein, Ingrid, Orly Elpeleg, Bruria Ben-Zeev, Stanley H. Korman, Alexander Lossos, Dorit Lev, Tally Lerman-Sagie, E. Leshinsky-Silver, Gerard Vockley, Gerard T. Berry, Anne-Marie Lamhownah, Dieter Matern, Charles R. Roe, Niels Gregersen l. 2008. “Short-chain acyl-CoA dehydrogenase gene mutation (319C>T) presents with clinical heterogeneity and is candidate founder mutation in Ashkenazi Jewish population” Molecular Genetics and Metabolism. 93(2):179-89. DOI:10.1016/j.ymgme.2007.09.021.
Tenopoulou, Margarita, Jie Chen, Jean Bastin, Michael J. Bennett, Harry Ischiropoulos, anPaschalis-Thomas Doulias. 2015. “Strategies for Correcting Very Long Chain Acyl-CoA Dehydrogenase Deficiency.” The Journal of Biological Chemistry. 290(16):10486-94. doi: 10.1074/jbc.M114.635102. The Journal of Lipid Research. 57:1329-38. doi: 10.1194/jlr.R067595.
Tucci, Sara, Sonja Pearson, Diran Herebian, Ute Spiekerkoetter. 2012. “Long-term, dietary effects on substrate selection and muscle fiber type in very-long-chain acyl-CoA dehydrogenase deficient (VLCAD -/-) mice.” Biochimica et Biophysica Acta. 1832(4):509-16. doi:10.1016/j.bbadis.2013.01.006.
Uppala R, McKinney RW, Brant KA, Fabisiak JP, Goetzman E.S. 2015. “Nickel inhibits mitochondrial fatty acid oxidation.” Biochemical and Biophysical Research Communications. 463(4):806-10. doi:10.1016/ j.bbrc.2015.06.017.
Uppala, Radha, Richard W. McKinney, Kelly A. Brant, James P. Fabisiak, Eric S. Goetzmn. 2015. “Nickel inhibits mitochondrial fatty acid oxidation.” Biochemical and Biophysical Research Communications, Vol.463, Issue 4: 806-810.
van Maldegem, BT, Duran M, Wanders RJ, Niezen-Koning KE, Hogeveen M, Ijlst L, Waterham HR, Wijburg FA. 2006. “Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency.” Journal of the American Medical Association. 296(8):943-52.
van Rijt W.J., Koolhaas G.D. Bekhof J., Heiner Fokkema M.R., de Koning T.J., Visser G., Schielen P.C.J.I., van Spronsen F.J., Derks T.G.J. 2016. “Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes.” Neonatology. 109:297-302. doi.org/10.1159/000443874.
Violante, Sara, Lodewijk IJIst, Henk van Lenthe, Isabel Tavares de Almeida, Ronald J. Wanders, Fatima V. Ventura. 2010. “Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling.” Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. Volume 1802, Issue 9: 728–732. http://dx.doi.org/10.1016/j.bbadis.2010.06.002.
Vockley, Jerry, Deborah Marsden, Elizabeth McCracken,Stephanie DeWard, Amanda Barone, Kristen Hsu, Emil Kakkis. “Long-term major clinical outcomes in patients with long chain fatty acid oxidation disorders before and after transition to triheptanoin – A retrospective chart review.” 2015. Molecular Genetics and Metabolism. 116(1-2):53-60. doi:10.1016/j.ymgme.2015.06.006.
Wajner, Moacir, Alexandre Umpierrez Amaral. 2016. “Mitochondrial dysfunction in fatty acid oxidation disorders: insights from human and animal studies.” Bioscience Reports. DOI: 10.1042/BSR20150240.
Wicks, Shawna, Bolormaa Vandanmagsar, Kimberly Haynie, Scott Fuller, Jaycob Warfel, Jacqueline Stephens, Miao Wang, Xianlin Han, Jingying Zhang, Robert Noland, and Randall Mynatt. 2015. “Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism.” Proceedings of the National Academy of Sciences (PNAS) 112(25):E3300-9. DOI:10.1073/pnas.1418560112.
Wilcken, Bridget, Piero Rinaldo, Dietrich Matern. 2006. “Newborn Screening for Inborn Errors of Metabolism.” In Inborn Metabolic Diseases, edited by
Fernandes, J.,
Saudubray, J.-M.,
Berghe, G. van D.,
Walter, J.H. Eds. 2006 75-86. Berlin Heidelberg: Springer-Verlag.
Wilcken, Bridget. 2010. “Fatty acid oxidation disorders: outcome and long-term prognosis.” Journal of Inherited Metabolic Disease, 2010 (33)5:501-506.
Wolfe, Lynne, Reena Jethva, Devin Oglesbee, and Jerry Vockley. 2014. “Short-Chain Acyl-CoA Dehydrogenase Deficiency.” In Gene Reviews. Edited by Adam MP, Ardinger HH, et al. Seattle: University of Washington. https://www.ncbi.nlm.nih.gov/books/NBK63582/? report=printable.
Yamada, Kenji, Hironori Kobayashi, Ryosuke Bo, Tomoo Takahashi, Jamiyan Purevsuren, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Takuya Ohkubo, Takanori Yokota, Mutsufusa Watanabe, Taiji Tsunemi, Hidehiro Mizusawa, Hiroshi Takuma, Ayako Shioya, Akiko Ishii, Akira Tamaoka, Yosuke Shigematsu, Hideo Sugie, Seiji Yamaguchi. 2016. “Clinical, biochemical and molecular investigation of adult-onset glutaric acidemia type II: Characteristics in comparison with pediatric cases.” Brain Development. 38(3):293–301. DOI: http://dx.doi.org/10.1016/j.braindev.2015.08.011.
Youngson, Robert M. 2004-2005. Collins Dictionary of Medicine. New York: Harper Collins. 704 pages.
Zand, Dina J., Kathleen M. Brown, Uta Lichter-Konecki, Joyce K. Campbell, Vesta Salehi, and James M. Chamberlain. 2008. “Effectiveness of a Clinical Pathway for the Emergency Treatment of Patients with Inborn Errors of Metabolism” Pediatrics. 122(6):1191-5. (Zand 2008,) doi: 10.1542/peds.2008-0205.
Zaugg, Kathrin, Yi Yao, Patrick T. Reilly, Karuppiah Kannan, Reza Kiarash, Jacqueline Mason, Ping Huang, Suzanne K. Sawyer, Benjamin Fuerth, Brandon Faubert, Tuula Kalliomäki, Andrew Elia, Xunyi Luo, Vincent Nadeem, David Bungard, Sireesha Yalavarthi, Joseph D. Growney, Andrew Wakeham, Yasmin Moolani, Jennifer Silvester, Annick You Ten, Walbert Bakker, Katsuya Tsuchihara, Shelley L. Berger, Richard P. Hill, Russell G. Jones, Ming Tsao, Murray O. Robinson, Craig B. Thompson, Guohua Pan, and Tak W. Mak. 2011. “Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress.” Genes & Development. 25(10):10411051.doi:10.1101/gad.1987211
Briefly, this will be most useful to primary level medical caregivers: doctors, nurses, emergency room personnel, neo-natal personnel, nutritionists, anyone with a patient who has one of these disorders or who might in the future have such a patient. It was written for the educated and/or highly motivated layperson who is either dealing with one of these disorders, or who has a family member who is.
Geneticists are NOT a good target audience as it was written for the layperson and purposely avoids the intricacies on which geneticists focus. They will find it elementary but may be willing to recommend it to families or primary-level physicians.
