Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD)
Homo sapiens
Disease Pathway
Created: 2013-08-29
Last Updated: 2022-12-07
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, which is also known LCHADD, is a rare inherited inborn error of metabolism (IEM) of long-chain fatty acid metabolism. The estimated birth prevalence of LCHADD is 1 in 62 000 in Northern European individuals. The worldwide birth prevalence is estimated at 1 in 250 000. MCADD is an autosomal recessive disorder associated with a mutation in the enzyme known as hydroxyacyl-CoA dehydrogenase (HADHA). HADHA catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. HADHA converts medium- and long-chain 2-enoyl-CoA compounds into the corresponding 3-ketoacyl-CoA compounds when NAD is present, and acetyl-CoA when NAD and CoASH are present. Deficiencies in this enzyme prevent the body from converting certain fats to energy, particularly during periods without food (fasting). Signs and symptoms of LCHAD deficiency typically manifest during infancy or early childhood and can include feeding difficulties, hypoglycemia, hypotonia, lethargy, liver problems, and retinal abnormalities. During late childhood, people may experience muscle pain and peripheral neuropathy. LCHAD-deficiency individuals are also at risk for breathing difficulties, serious heart problems, coma, and sudden death. Fasting or illnesses (e.g. viral infections) can trigger related problems. LCHADD is associated with some pregnancy-specific disorders, including preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), hyperemesis gravidarum, acute fatty liver of pregnancy, and maternal floor infarction of the placenta.
References
Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD) References
[Metagen: LONG-CHAIN-3-HYDROXYACYL-CoA DEHYDROGENASE DEFICIENCY (LCHAD)](http://metagene.de/program/d.prg?id_d=308)
[OMIM: 143450](http://omim.org/entry/143450})
[NIH](http://ghr.nlm.nih.gov/condition/long-chain-3-hydroxyacyl-coa-dehydrogenase-deficiency)
Sewell AC, Bender SW, Wirth S, Munterfering H, Ijlist L, Wanders RJ: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a severe fatty acid oxidation disorder. Eur J Pediatr. 1994 Oct;153(10):745-50.
Pubmed: 7813533
Fatty Acid Elongation in Mitochondria References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Lodish, H. et al. Molecular cell biology. (2004) New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D: An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature. 1997 Oct 16;389(6652):689-95. doi: 10.1038/39522.
Pubmed: 9338779
Miller AP, Willard HF: Chromosomal basis of X chromosome inactivation: identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8709-14. doi: 10.1073/pnas.95.15.8709.
Pubmed: 9671743
He XY, Schulz H, Yang SY: A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease. J Biol Chem. 1998 Apr 24;273(17):10741-6. doi: 10.1074/jbc.273.17.10741.
Pubmed: 9553139
Kamijo T, Aoyama T, Komiyama A, Hashimoto T: Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein. Biochem Biophys Res Commun. 1994 Mar 15;199(2):818-25. doi: 10.1006/bbrc.1994.1302.
Pubmed: 8135828
Zhang QX, Baldwin GS: Structures of the human cDNA and gene encoding the 78 kDa gastrin-binding protein and of a related pseudogene. Biochim Biophys Acta. 1994 Oct 18;1219(2):567-75. doi: 10.1016/0167-4781(94)90091-4.
Pubmed: 7918661
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Orii KE, Aoyama T, Wakui K, Fukushima Y, Miyajima H, Yamaguchi S, Orii T, Kondo N, Hashimoto T: Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency. Hum Mol Genet. 1997 Aug;6(8):1215-24. doi: 10.1093/hmg/6.8.1215.
Pubmed: 9259266
Janssen U, Davis EM, Le Beau MM, Stoffel W: Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural organization and assignment to chromosome 10q26.2-q26.3. Genomics. 1997 Mar 15;40(3):470-5. doi: 10.1006/geno.1996.4597.
Pubmed: 9073515
Peters H, Buck N, Wanders R, Ruiter J, Waterham H, Koster J, Yaplito-Lee J, Ferdinandusse S, Pitt J: ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. Brain. 2014 Nov;137(Pt 11):2903-8. doi: 10.1093/brain/awu216. Epub 2014 Aug 14.
Pubmed: 25125611
Haack TB, Jackson CB, Murayama K, Kremer LS, Schaller A, Kotzaeridou U, de Vries MC, Schottmann G, Santra S, Buchner B, Wieland T, Graf E, Freisinger P, Eggimann S, Ohtake A, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Sauer S, Memari Y, Kolb-Kokocinski A, Durbin R, Hasselmann O, Cremer K, Albrecht B, Wieczorek D, Engels H, Hahn D, Zink AM, Alston CL, Taylor RW, Rodenburg RJ, Trollmann R, Sperl W, Strom TM, Hoffmann GF, Mayr JA, Meitinger T, Bolognini R, Schuelke M, Nuoffer JM, Kolker S, Prokisch H, Klopstock T: Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement. Ann Clin Transl Neurol. 2015 May;2(5):492-509. doi: 10.1002/acn3.189. Epub 2015 Mar 13.
Pubmed: 26000322
Heimer G, Keratar JM, Riley LG, Balasubramaniam S, Eyal E, Pietikainen LP, Hiltunen JK, Marek-Yagel D, Hamada J, Gregory A, Rogers C, Hogarth P, Nance MA, Shalva N, Veber A, Tzadok M, Nissenkorn A, Tonduti D, Renaldo F, Kraoua I, Panteghini C, Valletta L, Garavaglia B, Cowley MJ, Gayevskiy V, Roscioli T, Silberstein JM, Hoffmann C, Raas-Rothschild A, Tiranti V, Anikster Y, Christodoulou J, Kastaniotis AJ, Ben-Zeev B, Hayflick SJ: MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder. Am J Hum Genet. 2016 Dec 1;99(6):1229-1244. doi: 10.1016/j.ajhg.2016.09.021. Epub 2016 Nov 3.
Pubmed: 27817865
Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W: Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res. 2000 May;10(5):703-13. doi: 10.1101/gr.10.5.703.
Pubmed: 10810093
Abe H, Ohtake A, Yamamoto S, Satoh Y, Takayanagi M, Amaya Y, Takiguchi M, Sakuraba H, Suzuki Y, Mori M, et al.: Cloning and sequence analysis of a full length cDNA encoding human mitochondrial 3-oxoacyl-CoA thiolase. Biochim Biophys Acta. 1993 Nov 16;1216(2):304-6. doi: 10.1016/0167-4781(93)90160-f.
Pubmed: 8241273
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Aboulaich N, Vainonen JP, Stralfors P, Vener AV: Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes. Biochem J. 2004 Oct 15;383(Pt 2):237-48. doi: 10.1042/BJ20040647.
Pubmed: 15242332
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings