Mitochondrial Fatty Acid Oxidation Disorders Associated with Short-Chain Enoyl-CoA Hydratase (ECHS1) Deficiency

Cells - Tập 7 Số 6 - Trang 46
Alice J. Sharpe1, Matthew McKenzie2,3
1Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, 3800 Melbourne, Australia
2Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, 3168 Melbourne, Australia
3Department of Molecular and Translational Science, Monash University, 3168 Melbourne, Australia

Tóm tắt

Mitochondrial fatty acid β-oxidation (FAO) is the primary pathway for fatty acid metabolism in humans, performing a key role in liver, heart and skeletal muscle energy homeostasis. FAO is particularly important during times of fasting when glucose supply is limited, providing energy for many organs and tissues, including the heart, liver and brain. Deficiencies in FAO can cause life-threatening metabolic disorders in early childhood that present with liver dysfunction, hypoglycemia, dilated hypertrophic cardiomyopathy and Reye-like Syndrome. Alternatively, FAO defects can also cause ‘milder’ adult-onset disease with exercise-induced myopathy and rhabdomyolysis. Short-chain enoyl-CoA hydratase (ECHS1) is a key FAO enzyme involved in the metabolism of fatty acyl-CoA esters. ECHS1 deficiency (ECHS1D) also causes human disease; however, the clinical manifestation is unlike most other FAO disorders. ECHS1D patients commonly present with Leigh syndrome, a lethal form of subacute necrotizing encephalomyelopathy traditionally associated with defects in oxidative phosphorylation (OXPHOS). In this article, we review the clinical, biochemical and genetic features of the ESHS1D patients described to date, and discuss the significance of the secondary OXPHOS defects associated with ECHS1D and their contribution to overall disease pathogenesis.

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Tài liệu tham khảo

McKenzie, 2016, Combined defects in oxidative phosphorylation and fatty acid beta-oxidation in mitochondrial disease, Biosci. Rep., 36, e00313, 10.1042/BSR20150295

Nunnari, 2012, Mitochondria: In Sickness and in Health, Cell, 148, 1145, 10.1016/j.cell.2012.02.035

Ouchida, 2017, The role of mitochondria in metabolism and cell death, Biochem. Biophys. Res. Commun., 482, 426, 10.1016/j.bbrc.2016.11.088

Koopman, 2013, OXPHOS mutations and neurodegeneration, EMBO J., 32, 9, 10.1038/emboj.2012.300

Smeitink, 2001, The genetics and pathology of oxidative phosphorylation, Nat. Rev. Genet., 2, 342, 10.1038/35072063

Wajner, 2016, Mitochondrial dysfunction in fatty acid oxidation disorders: Insights from human and animal studies, Biosci. Rep., 36, e00281, 10.1042/BSR20150240

Bartlett, 2004, Mitochondrial beta-oxidation, Eur. J. Biochem., 271, 462, 10.1046/j.1432-1033.2003.03947.x

Van Eunen, K., Volker-Touw, C.M.L., Gerding, A., Bleeker, A., Wolters, J.C., van Rijt, W.J., Martines, A.-C.M.F., Niezen-Koning, K.E., Heiner, R.M., and Permentier, H. (2016). Living on the edge: Substrate competition explains loss of robustness in mitochondrial fatty-acid oxidation disorders. BMC Biol., 14.

Carpenter, 1992, Human liver long-chain 3-hydroxyacyl-coenzyme a dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria, Biochem. Biophys. Res. Commun., 183, 443, 10.1016/0006-291X(92)90501-B

Kanazawa, 1993, Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase, Enzyme Protein, 47, 9, 10.1159/000468650

Davis, 1997, Human mitochondrial enoyl-CoA hydratase gene (ECHS1): Structural organization and assignment to chromosome 10q26. 2–q26. 3, Genomics, 40, 470, 10.1006/geno.1996.4597

Rabilloud, 2015, N-terminome analysis of the human mitochondrial proteome, Proteomics, 15, 2519, 10.1002/pmic.201400617

Hass, 1969, The subunit structure of crotonase, J. Biol. Chem., 244, 6080, 10.1016/S0021-9258(18)63508-2

Fong, 1977, Purification and properties of pig heart crotonase and the presence of short chain and long chain enoyl coenzyme A hydratases in pig and guinea pig tissues, J. Biol. Chem., 252, 542, 10.1016/S0021-9258(17)32751-5

Stern, 1953, Enzymatic reaction of crotonyl coenzyme A, J. Am. Chem. Soc., 75, 2277, 10.1021/ja01105a533

Yamada, 2015, Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: Significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion, J. Med. Genet., 52, 691, 10.1136/jmedgenet-2015-103231

Ferdinandusse, 2015, Clinical and biochemical characterization of four patients with mutations in ECHS1, Orphanet J. Rare Dis., 10, 79, 10.1186/s13023-015-0290-1

DiMauro, 1973, Muscle carnitine palmityltransferase deficiency and myoglobinuria, Science, 182, 929, 10.1126/science.182.4115.929

Karpati, 1975, The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical, and pathophysiologic features, Neurology, 25, 16, 10.1212/WNL.25.1.16

Gregersen, 1976, Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria, Clin. Chim. Acta, 70, 417, 10.1016/0009-8981(76)90355-7

Kelly, 1990, Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency, Proc. Natl. Acad. Sci. USA, 87, 9236, 10.1073/pnas.87.23.9236

Yokota, 1990, Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation, J. Clin. Investig., 86, 1000, 10.1172/JCI114761

Matsubara, 1990, Molecular lesion in patients with medium-chain acyl-CoA dehydrogenase deficiency, Lancet, 335, 1589, 10.1016/0140-6736(90)91413-5

Houten, 2016, The Biochemistry and Physiology of Mitochondrial Fatty Acid beta-Oxidation and Its Genetic Disorders, Annu. Rev. Physiol., 78, 23, 10.1146/annurev-physiol-021115-105045

Kompare, 2008, Mitochondrial fatty-acid oxidation disorders, Semin. Pediatr. Neurol., 15, 140, 10.1016/j.spen.2008.05.008

Tyni, 1999, Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, Acta Paediatr., 88, 237, 10.1111/j.1651-2227.1999.tb01089.x

Houten, 2010, A general introduction to the biochemistry of mitochondrial fatty acid beta-oxidation, J. Inherit. Metab. Dis., 33, 469, 10.1007/s10545-010-9061-2

Giurgea, 2004, Neonatal hypoglycaemia: Aetiologies, Semin. Neonatol., 9, 49, 10.1016/j.siny.2003.08.002

Kottlors, 2001, Valproic acid triggers acute rhabdomyolysis in a patient with carnitine palmitoyltransferase type II deficiency, Neuromuscul. Disord., 11, 757, 10.1016/S0960-8966(01)00228-0

Moczulski, 2009, An overview of beta-oxidation disorders, Postepy Hig. Med. Dosw., 63, 266

Emery, 1988, Investigation of inborn errors of metabolism in unexpected infant deaths, Lancet, 2, 29, 10.1016/S0140-6736(88)92955-8

Wanders, 1989, Sudden infant death and long-chain 3-hydroxyacyl-CoA dehydrogenase, Lancet, 2, 52, 10.1016/S0140-6736(89)90300-0

Sim, 2002, Strategies for the diagnosis of mitochondrial fatty acid beta-oxidation disorders, Clin. Chim. Acta, 323, 37, 10.1016/S0009-8981(02)00182-1

Mansouri, 1996, Assessment of the prevalence of genetic metabolic defects in acute fatty liver of pregnancy, J. Hepatol., 25, 781, 10.1016/S0168-8278(96)80254-6

Shamseldin, 2017, A lethal neonatal phenotype of mitochondrial short-chain enoyl-CoA hydratase-1 deficiency, Clin. Genet., 91, 629, 10.1111/cge.12891

Aulbert, 2014, Long survival in Leigh syndrome: New cases and review of literature, Neuropediatrics, 45, 346, 10.1055/s-0034-1383823

Saudubray, 1999, Recognition and management of fatty acid oxidation defects: A series of 107 patients, J. Inherit. Metab. Dis., 22, 488, 10.1023/A:1005556207210

Lake, 2016, Leigh syndrome: One disorder, more than 75 monogenic causes, Ann. Neurol., 79, 190, 10.1002/ana.24551

Rahman, 1996, Leigh syndrome: Clinical features and biochemical and DNA abnormalities, Ann. Neurol., 39, 343, 10.1002/ana.410390311

Haack, 2015, Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement, Ann. Clin. Transl. Neurol., 2, 492, 10.1002/acn3.189

Mahajan, 2017, ECHS1 deficiency-associated paroxysmal exercise-induced dyskinesias: Case presentation and initial benefit of intervention, J. Neurol., 264, 185, 10.1007/s00415-016-8381-z

Olgiati, 2016, Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency, Mov. Disord., 31, 1041, 10.1002/mds.26610

Balasubramaniam, 2017, Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency, J. Inherit. Metab. Dis., 40, 745, 10.1007/s10545-017-0036-4

Bhatia, 2011, Paroxysmal dyskinesias, Mov. Disord., 26, 1157, 10.1002/mds.23765

Peters, 2014, ECHS1 mutations in Leigh disease: A new inborn error of metabolism affecting valine metabolism, Brain, 137, 2903, 10.1093/brain/awu216

Nair, 2016, Novel ECHS1 mutation in an Emirati neonate with severe metabolic acidosis, Metab. Brain Dis., 31, 1189, 10.1007/s11011-016-9842-x

Tetreault, 2015, Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome, Hum. Genet., 134, 981, 10.1007/s00439-015-1577-y

Fitzsimons, 2018, Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency, Am. J. Med. Genet. A, 176, 1115, 10.1002/ajmg.a.38658

Sakai, 2015, ECHS1 mutations cause combined respiratory chain deficiency resulting in leigh syndrome, Hum. Mutat., 36, 232, 10.1002/humu.22730

Ganetzky, 2016, ECHS1 Deficiency as a Cause of Severe Neonatal Lactic Acidosis, JIMD Rep., 30, 33, 10.1007/8904_2016_538

Bedoyan, 2017, Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency, Mol. Genet. Metab., 120, 342, 10.1016/j.ymgme.2017.02.002

Huffnagel, 2017, Mitochondrial Encephalopathy and Transient 3-Methylglutaconic Aciduria in ECHS1 Deficiency: Long-Term Follow-Up, JIMD Rep., 39, 83, 10.1007/8904_2017_48

Ogawa, 2017, Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: A study of 106 Japanese patients, J. Inherit. Metab. Dis., 40, 685, 10.1007/s10545-017-0042-6

Peters, 2015, Metabolite studies in HIBCH and ECHS1 defects: Implications for screening, Mol. Genet. Metab., 115, 168, 10.1016/j.ymgme.2015.06.008

Brown, 1982, β-Hydroxyisobutyryl coenzyme A deacylase deficiency: A defect in valine metabolism associated with physical malformations, Pediatrics, 70, 532, 10.1542/peds.70.4.532

Sumegi, 1984, Complex I binds several mitochondrial NAD-coupled dehydrogenases, J. Biol. Chem., 259, 15040, 10.1016/S0021-9258(17)42511-7

Parker, 2000, Preliminary evidence for the existence of specific functional assemblies between enzymes of the beta-oxidation pathway and the respiratory chain, Biochem. J., 345, 429, 10.1042/bj3450429

Wang, 2010, Evidence for physical association of mitochondrial fatty acid oxidation and oxidative phosphorylation complexes, J. Biol. Chem., 285, 29834, 10.1074/jbc.M110.139493

Das, 2000, Secondary respiratory chain defect in a boy with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: Possible diagnostic pitfalls, Eur. J. Pediatr., 159, 243, 10.1007/s004310050063

Lim, 2018, Loss of the Mitochondrial Fatty Acid β-Oxidation Protein Medium-Chain Acyl-Coenzyme A Dehydrogenase Disrupts Oxidative Phosphorylation Protein Complex Stability and Function, Sci. Rep., 8, 153, 10.1038/s41598-017-18530-4