Mitochondrial disorders. A diagnostic challenge in clinical chemistry

Clinical Chemistry and Laboratory Medicine

Volumn 37, Issue 9, 1999, Pages 855-876

  Bauer, Matthias F ^a,b   Gempel, Klaus ^a   Hofmann, Sabine ^a   Jaksch, Michaela ^a   Philbrook, Christine ^a   Gerbitz, Klaus Dieter ^a  

^a Academic Hospital   (Germany)

^b Klinikum Schwabing   (Germany)

Author keywords

Diagnostic of mitochondrial diseases; Fatty acid and amino acid degradation defects; Mitochondrial disorders; mtDNA; Mutational analysis; Tandem mass spectrometry

Indexed keywords

BIOGENESIS; CARNITINE DEFICIENCY; CELL METABOLISM; DISORDERS OF MITOCHONDRIAL FUNCTIONS; FRIEDREICH ATAXIA; GENETIC COUNSELING; GENETIC DISORDER; GENETIC HETEROGENEITY; HUMAN; LEIGH DISEASE; METABOLISM; MISSENSE MUTATION; MITOCHONDRIAL RESPIRATION; MOLECULAR GENETICS; OXIDATIVE PHOSPHORYLATION; PHENOTYPE; PRENATAL DIAGNOSIS; PRIORITY JOURNAL; REVIEW; SOMATIC MUTATION; SPASTIC PARAPLEGIA; TANDEM MASS SPECTROMETRY; WILSON DISEASE;

CHEMISTRY, CLINICAL; HUMANS; MITOCHONDRIAL MYOPATHIES; MODELS, BIOLOGICAL;

EID: 0032722723     PISSN: 14346621     EISSN: None     Source Type: Journal    
DOI: 10.1515/CCLM.1999.129     Document Type: Review

References (207)

1. Holt IJ, Harding AE, Morgan-Hughes JA. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 1988; 331:717-9.
2. Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 1988; 242:1427-30.
3. Kogelnik AM, Lott MT, Brown MD, Navathe SB, Wallace DC. MITOMAP: a human mitochondrial genome database - 1998 update. Nucleic Acids Res 1998; 26:112-5.
4. Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Pequignot E, et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995; 11:144-9.
5. Loeffen J, Smeitink J, Triepels R, Smeets R, Schuelke M, Sengers R, et al. The first nuclear-encoded complex I mutation in a patient with Leigh syndrome. Am J Hum Genet 1998; 63:1598-608.
6. van den Heuvel L, Ruitenbeek W, Smeets R, Gelman-Kohan Z, Elpeleg O, Loeffen J, et al. Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit. Am J Hum Genet 1998; 62:262-8.
7. Schuelke M, Smeitink J, Mariman E, Loeffen J, Plecko B, Trijbels F, et al. Mutant NDUFV1 subunit of mitochondria I complex I causes leukodystrophy and myoclonic epilepsy. Nat Genet 1999; 21:260-1.
8. Tiranti V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M, et al. Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. Am J Hum Genet 1998; 63:1609-21.
9. Zhu Z, Yao J, Johns T, Fu K, De Bie I, Macmillan C, et al. SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nat Genet 1998; 20:337-43.
10. Koutnikova H, Campuzano V, Foury F, Dolle P, Cazzalini O, Koenig M. Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nat Genet 1997; 16:345-51.
11. Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 1998; 93:973-83.
12. Lutsenko S, Cooper MJ. Localization of the Wilson's disease protein product to mitochondria. Proc Natl Acad Sci USA 1998; 95:6004-9.
13. Koehler CM, Leuenberger D, Merchant S, Renold A, Junne T, Schatz G. Human deafness dystonia syndrome is a mitochondrial disease. Proc Natl Acad Sci USA 1999; 96:2141-6.
14. Tatton WG, Olanow CW. Apoptosis in neu rodegenerative diseases: the role of mitochondria. Biochim Biophys Acta 1999; 1410:195-213.
15. Cortopassi GA, Wong A. Mitochondria in organismal aging and degeneration. Biochim Biophys Acta 1999; 1410:183-93.
16. Gerbitz KD, Gempel K, Brdiczka D. Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit. Diabetes 1996; 45:113-26.
17. Taylor KD, Piko L. Patterns of mRNA prevalence and expression of B1 and B2 transcripts in early mouse embryos. Development 1987; 101:877-92.
18. Piko L, Taylor KD. Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Dev Biol 1987; 123:364-74.
19. Wallace DC. Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci USA 1994; 91:8739-46.
20. Bauer MF, Neupert W. Protein Transport Across the Outer and Inner Membranes of Mitochondria. In: Konings HR, Kaback JS, Lolkema M, editors. Handbook of Biological Physics. Volume 2. Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo: Elsvier; 1996:791 pp.
21. Neupert W. Protein import into mitochondria. Annu Rev Biochem 1997; 66:863-917.
22. Rassow J, Dekker PJT, van Wilpe S, Meijer M, Soll J. The preprotein translocase of the mitochondrial inner membrane: function and evolution. J Mol Biol 1999; 286:105-20.
23. Bauer MF, Sirrenberg C, Neupert W, Brunner M. Role of TIM23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell 1996; 87:33-41.
24. Berthold J, Bauer MF, Schneider H-C, Klaus C, Dietmeier K, Neupert W, et al. The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ATP driving system. Cell 1995; 81:1085-93.
25. Kronidou NG, Oppliger W, Bolliger L, Hannavy K, Glick BS, Schatz G, et al. Dynamic interaction between Isp45 and mitochondrial hsp70 in the protein import system of the yeast mitochondrial inner membrane. Proc Natl Acad Sci USA 1994; 91:12818-22.
26. Rassow J, Maarse AC, Krainer E, Kübrich M, Müller H, Meijer M, et al. Mitochondrial protein import: Biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44. J Cell Biol 1994; 127:1547-56.
27. Schneider H-C, Berthold J, Bauer MF, Dietmeier K, Guiard B, Brunner M, et al. Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature 1994; 371:768-74.
28. Sirrenberg C, Bauer MF, Guiard B, Neupert W, Brunner M. Import of carrier proteins into the mitochondrial inner membrane mediated by TIM22. Nature 1996; 384:582-5.
29. Sirrenberg C, Endres M, Becker K, Bauer MF, Walther E, Neupert W, et al. Functional cooperation and stoichiometry of protein translocases of the outer and inner membranes of mitochondria. J Biol Chem 1997; 272:29963-6.
30. Sirrenberg C, Endres M, Folsch H, Stuart RA, Neupert W, Brunner M. Carrier protein import into mitochondria mediated by the intermembrane proteins TIM10/Mrs11 and TIM12/Mrs5. Nature 1998; 391:912-5.
31. Nelson DR, Felix CM, Swanson JM. Highly conserved charge-pair networks in the mitochondrial carrier family. J Mol Biol 1998; 277:285-308.
32. Kerscher O, Holder J, Srinivasan M, Leung RS, Jensen RE. The TIM54p-TIM22p complex mediates insertion of proteins into the mitochondrial inner membrane. J Cell Biol 1997; 139:1663-75.
33. Koehler CM, Merchant S, Oppliger W, Schmid K, Jarosch E, Dolfini L, et al. TIM9p, an essential partner subunit of TIM10p for the import of mitochondrial carrier proteins. Embo J 1998; 17:6477-86.
34. Bauer M, Gempel K, Reichert A, Rappold G, Lichter P, Gerbitz K-D, et al. Genetic and structural characterization of the human mitochondrial inner membrane translocase. J Mol Biol 1999; 289:69-82.
35. Bauer MF, Hofmann S, Neupert W, Brunner M. Protein translocation into mitochondria: the role of TIM complexes. Trends Cell Biol 1999; in press.
36. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature 1981; 290:457-65.
37. Wallace DC, Lott MT, Shoffner JM, Brown MD. Diseases resulting from mitochondrial DNA point mutations. J Inherit Metab Dis 1992; 15:472-9.
38. Brown MD, Torroni A, Shoffner JM, Wallace DC. Mitochondrial tRNA(Thr) mutations and lethal infantile mitochondrial myopathy. Am J Hum Genet 1992; 51:446-7.
39. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993; 90:7915-22.
40. Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 1980; 77:6715-9.
41. Wallace DC. Mitochondrial DNA mutations in diseases of energy metabolism. J Bioenerg Biomembr 1994; 26:241-50.
42. Shoffner JM. Maternal inheritance and the evaluation of oxidative phosphorylation diseases. Lancet 1996; 348:1283-8.
43. Lightowlers RN, Jacobs HT, Kajander OA. Mitochondrial DNA-all things bad? Trends in Genetics 1999; 15:91-93.
44. Nicholls D, Ferguson S. Bioenergetics 2. London, San Diego, New York: Academic Press; 1992.
45. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281:1309-12.
46. Walker JE. Determination of the structures of respiratory enzyme complexes from mammalian mitochondria. Biochim Biophys Acta 1995; 1271:221-7.
47. Abrahams JP, Leslie AG, Lutter R, Walker JE. Structure at 2.8 A resolution of F1-ATPase from bovine heart mitochondria. Nature 1994; 370:621-8.
48. Walker JE, Collinson IR, Van Raaij MJ, Runswick MJ. Structural analysis of ATP synthase from bovine heart mitochondria. Methods Enzymol 1995; 260:163-90.
49. Leslie AG, Abrahams JP, Braig K, Lutter R, Menz RI, Orriss GL, et al. The structure of bovine mitochondrial F1-ATPase: an example of rotary catalysis. Biochem Soc Trans 1999; 27:37-42.
50. Eaton S, Bartlett K, Pourfarzam M. Mammalian mitochondrial beta-oxidation. Biochem J 1996; 320:345-57.
51. Bremer J. Carnitine-metabolism and functions. Physiol Rev 1983; 63:1420-80.
52. Stakkestad JA, Bremer J. The outer carnitine palmitoyltransferase and regulation of fatty acid metabolism in rat liver in different thyroid states. Biochim Biophys Acta 1983; 750:244-52.
53. Lund H, Bremer J. Carnitine acetyltransferase. Effect of malonyl-CoA, fasting and clofibrate feeding in mitochondria from different tissues. Biochim Biophys Acta 1983; 750:164-70.
54. Indiveri C, Palmieri F. Purification and reconstitution of the carnitine carrier from rat liver mitochondria. Ital J Biochem 1990; 39:165A-7A.
55. Indiveri C, Iacobazzi V, Giangregorio N, Palmieri F. The mitochondrial carnitine carrier protein: cDNA cloning, primary structure and comparison with other mitochondrial transport proteins. Biochem J 1997; 321:713-9.
56. Palmieri F, Bisaccia F, Capobianco L, Dolce V, Fiermonte G, Iacobazzi V, et al. Mitochondrial metabolite transporters. Biochim Biophys Acta 1996; 1275:127-32.
57. Huizing M, Iacobazzi V, Ijlst L, Savelkoul P, Ruitenbeek W, van den Heuvel L, et al. Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am J Hum Genet 1997; 61:1239-45.
58. Ijlst L, Wanders RJ, Ushikubo S, Kamijo T, Hashimoto T. Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein. Biochim Biophys Acta 1994; 1215:347-50.
59. Jackson S, Schaefer J, Middleton B,Turnbull DM. Characterisation of a novel enzyme of human fatty acid beta-oxidation: a matrix-associated, mitochondrial 2-enoyl-CoA hydratase. Biochem Biophys Res Commun 1995; 214:247-53.
60. Ikeda Y, Tanaka K. Purification and characterization of 2-methyl-branched chain acyl coenzyme A dehydrogenase, an enzyme involved in the isoleucine and valine metabolism, from rat liver mitochondria. J Biol Chem 1983; 258:9477-87.
61. Lynen F, Knappe J, Lorch E, Jutting G, Ringelmann E, Lachance JP. Zur biochemischen Funktion des Biotins II: Reinigung und Wirkungsweise der beta-Methyl-crotonyl-Carboxylase. Biochem Z 1961; 335:123.
62. Narisawa K, Gibson KM, Sweetman L, Nyhan WL, Duran M, Wadman SK. Deficiency of 3-methylglutaconyl-coenzyme A hydratase in two siblings with 3-methylglutaconic aciduria. J Clin Invest 1986; 77:1148-52.
63. Kramθr PR, Miziorko HM. Purification and characterization of avian liver 3-hydroxy-3- methylglutaryl coenzyme A lyase. J Biol Chem 1980; 255:11023-8.
64. Ikeda Y, Tanaka K. Purification and characterization of isovaleryl coenzyme A dehydrogenase from rat liver mitochondria. J Biol Chem 1983; 258:1077-85.
65. Fukao T, Yamaguchi S, Kano M, Orii T, Fujiki Y, Osumi T, et al. Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency. J Clin Invest 1990; 86:2086-92.
66. Hsia YE, Scully KJ, Rosenberg LE. Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. Pediatr Res 1979; 13:746-51.
67. Mazumder R, Sasakawa T, Kaziro Y, Ochoa S. Metabolism of propionic acid in animal tissues. IX. Methylmalonyl coenzyme A racemase. J Biol Chem 1962; 237:3065.
68. Kolhouse JF, Utley C, Allen RH. Isolation and characterization of methylmalonyl-CoA mutase from human placenta. J Biol Chem 1980; 255:2708-12.
69. Goodman IS, Frerman FE. Organic acidemias due to defects in lysine oxidation: 2-Ketoadipic acidemia and glutaric acidemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. 7 ed. New York: McGraw-Hill; 1995: 1451-60.
70. Goodman SI, Kratz LE, DiGiulio KA, Biery BJ, Goodman KE, Isaya G, et al. Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli. Hum Mol Genet 1995; 4:1493-8.
71. Wallace DC. 1994 William Allan Award Address. Mitochondrial DNA variation in human evolution, degenerative disease, and aging. Am J Hum Genet 1995; 57:201-23.
72. Howell N. Leber hereditary optic neuropathy: respiratory chain dysfunction and degeneration of the optic nerve. Vision Res 1998; 38:1495-504.
73. Howell N, Bindoff LA, McCullough DA, Kubacka I, Poulton J, Mackey D, et al. Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am J Hum Genet 1991; 49:939-50.
74. Huoponen K, Vilkki J, Aula P, Nikoskelainen EK, Savontaus ML. A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy. Am J Hum Genet 1991; 48:1147-53.
75. Howell N, Kubacka I, Xu M, McCullough DA. Leber hereitary optic neuropathy: involvement of the mitochondrial ND1 gene and evidence for an intragenic suppressor mutation. Am J Hum Genet 1991; 48:935-42.
76. Howell N, Kubacka I, Halvorson S, Howell B, McCullough DA, Mackey D. Phylogenetic analysis of the mitochondrial genomes from Leber hereditary optic neuropathy pedigrees. Genetics 1995; 140:285-302.
77. Johns DR, Smith KH, Miller NR. Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation. Arch Ophthalmol 1992; 110:1577-81.
78. Howell N, Kubacka I, Halvorson S, Mackey D. Leber's hereditary optic neuropathy: the etiological role of a mutation in the mitochondrial cytochrome b gene. Genetics 1993; 133:133-6.
79. Johns DR, Neufeld MJ, Park RD. An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem Biophys Res Commun 1992; 187:1551-7.
80. Torroni A, Petrozzi M, D'Urbano L, Sellitto D, Zeviani M, Carrara F, et al. Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am J Hum Genet 1997; 60:1107-21.
81. Hofmann S, Jaksch M, Bezold R, Mertens S, Aholt S, Paprotta A, et al. Population genetics and disease susceptibility: characterization of central European haplogroups by mtDNA gene mutations, correlation with D loop variants and association with disease. Hum Mol Genet 1997; 6:1835-46.
82. Hofmann S, Bezold R, Jaksch M, Obermaier-Kusser B, Mertens S, Kaufhold P, et al. Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes. Genomics 1997; 39:8-18.
83. Jun AS, Brown MD, Wallace DC. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia. Proc Natl Acad Sci USA 1994; 91:6206-10.
84. Wallace DC, Murdock DG. Mitochondria and dystonia: the movement disorder connection? Proc Natl Acad Sci USA 1999; 96:1817-9.
85. Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 1990; 348:651-3.
86. Kobayashi Y, Momoi MY, Tominaga K, Momoi T, Nihei K, Yanagisawa M, et al. A point mutation in the mitochondrial tRNA(Leu)(UUR) gene in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Biochem Biophys Res Commun 1990; 173:816-22.
87. Zeviani M, Gellera C, Antozzi C, Rimoldi M, Morandi L, Villani F, et al. Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA(Leu)(UUR). Lancet 1991; 338:143-7.
88. Enter C, Muller-Hocker J, Zierz S, Kurlemann G, Pongratz D, Forster C, et al. A specific point mutation in the mitochondrial genome of Caucasians with MELAS. Hum Genet 1991 ; 88:233-6.
89. Obermaier-Kusser B, Paetzke-Brunner I, Enter C, Muller-Hocker J, Zierz S, Ruitenbeek W, et al. Respiratory chain activity in tissues from patients (MELAS) with a point mutation of the mitochondrial genome [tRNA(Leu(UUR))]. FEBS Lett 1991; 286:67-70.
90. Campos Y, Martin MA, Lorenzo G, Aparicio M, Cabello A, Arenas J. Sporadic MERRF/MELAS overlap syndrome associated with the 3243 tRNA(Leu(UUR)) mutation of mitochondrial DNA. Muscle Nerve 1996; 19:187-90.
91. Vilarinho L, Santorelli FM, Rosas MJ, Tavares C, Melo-Pires M, DiMauro S. The mitochondrial A3243G mutation presenting as severe cardiomyopathy. J Med Genet 1997; 34:607-9.
92. Verma A, Moraes CT, Shebert RT, Bradley WG. A MERRF/PEO overlap syndrome associated with the mitochondrial DNA 3243 mutation. Neurology 1996; 46:1334-6.
93. Jaksch M, Hofmann S, Kaufhold P, Obermaier-Kusser B, Zierz S, Gerbitz KD. A novel combination of mitochondrial tRNA and NDI gene mutations in a syndrome with MELAS, cardiomyopathy, and diabetes mellitus. Hum Mutat 1996; 7:358-60.
94. Morten KJ, Cooper JM, Brown GK, Lake BD, Pike D, Poulton J. A new point mutation associated with mitochondrial encephalomyopathy. Hum Mol Genet 1993; 2:2081-7.
95. Sato W, Hayasaka K, Shoji Y, Takahashi T, Takada G, Saito M, et al. A mitochondrial tRNA(Leu)(UUR) mutation at 3,256 associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochem Mol Biol Int 1994; 33:1055-61.
96. Goto Y, Nonaka I, Horai S. A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Biochim Biophys Acta 1991; 1097:238-40.
97. Goto Y, Tsugane K, Tanabe Y, Nonaka I, Horai S. A new point mutation at nucleotide pair 3291 of the mitochondrial tRNA(Leu(UUR)) gene in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochem Biophys Res Commun 1994; 202:1624-30.
98. van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1992; 1:368-71.
99. Gerbitz KD, Paprotta A, Jaksch M, Zierz S, Drechsel J. Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNALeu(UUR) gene. FEBS Lett 1993; 321:194-6.
100. van den Ouweland JM, Lemkes HH, Trembath RC, Ross R, Velho G, Cohen D, et al. Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes 1994; 43:746-51.
101. Gerbitz KD, van den Ouweland JM, Maassen JA, Jaksch M. Mitochondrial diabetes mellitus: a review. Biochim Biophys Acta 1995; 1271:253-60.
102. Wallace DC, Zheng XX, Lott MT, Shoffner JM, Hodge JA, Kelley RI, et al. Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 1988; 55:601-10.
103. Wallace DC. Mitochondrial Diseases in Man and Mouse. Science 1999; 283:1482-1488.
104. Tiranti V, Chariot P, Carella F, Toscano A, Soliveri P, Girlanda P, et al. Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNASer(UCN) gene. Hum Mol Genet 1995; 4:1421-7.
105. Jaksch M, Klopstock T, Kurlemann G, Dorner M, Hofmann S, Kleinle S, et al. Progressive myoclonus epilepsy and mitochondrial myopathy associated with mutations in the tRNA(Ser(UCN)) gene. Ann Neurol 1998; 44:635-40.
106. Ozawa M, Nishino I, Horai S, Nonaka I, Goto YI. Myoclonus epilepsy associated with ragged-red fibers: a G-to-A mutation at nucleotide pair 8363 in mitochondrial tRNA(Lys) in two families. Muscle Nerve 1997; 20:271-8.
107. Reid FM, Vernham GA, Jacobs HT. A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness. Hum Mutat 1994; 3:243-7.
108. Nakamura M, Nakano S, Goto Y, Ozawa M, Nagahama Y, Fukuyama H, et al. A novel point mutation in the mitochondrial tRNA(Ser(UCN)) gene detected in a family with MERRF/MELAS overlap syndrome. Biochem Biophys Res Commun 1995; 214:86-93.
109. Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic- induced and non-syndromic deafness. Nat Genet 1993; 4:289-94.
110. Estivill X, Govea N, Barceló A, Perelló E, Badenas C, Romero E, et al. Familial Progressive Sensorineural Deafness Is Mainly Due to the mtDNA A1555G Mutation and Is Enhanced by Treatment with Aminoglycosides. Am J Hum Genet 1997; 62:27-35.
111. Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 1989; 320:1293-9.
112. Rotig A, Cormier V, Blanche S, Bonnefont JP, Ledeist F, Romero N, et al. Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 1990;86:1601-8.
113. Rotig A, Cormier V, Chatelain P, Francois R, Saudubray JM, Rustin P, et al. Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). J Clin Invest 1993; 91:1095-8.
114. Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, et al. Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1992; 1:11-5.
115. Ballinger SW, Shoffner JM, Gebhart S, Koontz DA, Wallace DC. Mitochondrial diabetes revisited. Nat Genet 1994; 7:458-9.
116. Papadimitriou A, Hadjigeorgiou GM, Divari R, Papagalanis N, Comi G, Bresolin N. The influence of Coenzyme Q10 on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism. Neuromuscul Disord 1996; 6:49-53.
117. Tulinius MH, Oldfors A, Holme E, Larsson NG, Houshmand M, Fahleson P, et al. Atypical presentation of multi-system disorders in two girls with mitochondrial DNA deletions. Eur J Pediatr 1995; 154:35-42.
118. Chen CM, Huang CC. Gonadal dysfunction in mitochondrial encephalomyopathies. Eur Neurol 1995; 35:281-6.
119. St. John JC, Cooke ID, Barratt CL. Mitochondrial mutations and male infertility. Nat Med 1997; 3:124-5.
120. Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, et al. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 1998; 20:291-3.
121. Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat Res 1992; 275:169-80.
122. Soong NW, Hinton DR, Cortopassi G, Arnheim N. Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain. Nat Genet 1992; 2:318-23.
123. Cortopassi GA, Shibata D, Soong NW, Arnheim N. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci U S A 1992; 89:7370-4.
124. Melov S, Hinerfeld D, Esposito L, Wallace DC. Multi-organ characterization of mitochondrial genomic rearrangements in ad libitum and caloric restricted mice show striking somatic mitochondrial DNA rearrangements with age. Nucleic Acids Res 1997; 25:974-82.
125. Leigh D. Subacute necrotizing encephalomyelopathy in an infant. 1951. J Neurol Neurosurg Psychiat 1951; 14.
126. Rahman S, Blok RB, Dahl HH, Danks DM, Kirby DM, Chow CW, et al. Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol 1996; 39:343-51.
127. Dahl HH. Getting to the nucleus of mitochondrial disorders: identification of respiratory chain-enzyme genes causing Leigh syndrome. Am J Hum Genet 1998; 63:1594-7.
128. Poyton RO. Assembling a time bomb-cytochrome c oxidase and disease. Nat Genet 1998; 20:316-7.
129. DiMauro S, De Vivo DC. Genetic heterogeneity in Leigh syndrome. Ann Neurol 1996; 40:5-7.
130. Willems JL, Monnens LA, Trijbels JM, Veerkamp JH, Meyer AE, van Dam K, et al. Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics 1977; 60:850-7.
131. Jaksch M, Hofmann S, Kleinle S, Liechti-Gallati S, Pongratz DE, Muller-Hocker J, et al. A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNA(Ser)(UCN) mutations in a subgroup with syndromal encephalopathy. J Med Genet 1998; 35:895-900.
132. Adams PL, Lightowlers RN, Turnbull DM. Molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome. Ann Neurol 1997; 41:268-70.
133. Tiranti V, Jaksch M, Hofmann S, Galimberti C, Uziel G, Bezold R, et al. Loss-of-function mutations of SURF-1 are speicifcally associated with Leigh syndrome with cytochrome c oxidase deficiency. Ann Neurol 1999; 46:161-6.
134. Mashkevich G, Repetto B, Glerum DM, Jin C, Tzagoloff A. SHY1, the yeast homolog of the mammalian SURF-1 gene, encodes a mitochondrial protein required for respiration. J Biol Chem 1997; 272:14356-64.
135. Dionisi-Vici C, Seneca S, Zeviani M, Fariello G, Rimoldi M, Bertini E, et al. Fulminant Leigh syndrome and sudden unexpected death in a family with the T9176C mutation of the mitochondrial ATPase 6 gene. J Inherit Metab Dis 1998; 21:2-8.
136. De Meirleir L, Lissens W, Benelli C, Ponsot G, Desguerre I, Marsac C, et al. Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy. Pediatr Res 1994; 36:707-12.
137. Dahl HH. Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again. Am J Hum Genet 1995; 56:553-7.
138. Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, et al. cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed. Biochem Biophys Res Commun 1998; 253:415-22.
139. Harding AE. Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry 1981; 44:871-83.
140. Durr A, Brice A, Serdaru M, Rancurel G, Derouesne C, Lyon-Caen O, et al. The phenotype of "pure" autosomal dominant spastic paraplegia. Neurology 1994; 44:1274-7.
141. Reid E. Pure hereditary spastic paraplegia. J Med Genet 1997; 34:499-503.
142. Hazan J, Fontaine B, Bruyn RP, Lamy C, van Deutekom JC, Rime CS, et al. Linkage of a new locus for autosomal dominant familial spastic paraplegia to chromosome 2p. Hum Mol Genet 1994; 3:1569-73.
143. Hazan J, Lamy C, Melki J, Munnich A, de Recondo J, Weissenbach J. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet 1993; 5:163-7.
144. Fink JK. Advances in hereditary spastic paraplegia. Curr Opin Neurol 1997; 10:313-8.
145. Savel'ev AS, Novikova LA, Kovaleva IE, Luzikov VN, Neupert W, Langer T. ATP-dependent proteolysis in mitochondria. m-AAA protease and PIM1 protease exert overlapping substrate specificities and cooperate with the mtHsp70 system. J Biol Chem 1998; 273:20596-602.
146. Arlt H, Steglich G, Perryman R, Guiard B, Neupert W, Langer T. The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease. Embo J 1998; 17:4837-47.
147. Leonhard K, Herrmann JM, Stuart RA, Mannhaupt G, Neupert W, Langer T. AAA proteases with catalytic sites on opposite membrane surfaces comprise a proteolytic system for the ATP-dependent degradation of inner membrane proteins in mitochondria. Embo J 1996; 15:4218-29.
148. Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271:1423-7.
149. Wilson RB, Roof DM. Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nat Genet 1997; 16:352-7.
150. Wong A, Yang J, Cavadini P, Gellera C, Lonnerdal B, Taroni F, et al. The Friedreich's ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis. Hum Mol Genet 1999; 8:425-430.
151. Jin H, May M, Tranebjaerg L, Kendall E, Fontan G, Jackson J, et al. A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness. Nat Genet 1996; 14:177-80.
152. Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S. An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 1989; 339:309-11.
153. Zeviani M, Bresolin N, Gellera C, Bordoni A, Pannacci M, Amati P, et al. Nucleus-driven multiple large-scale deletions of the human mitochondrial genome:a newautosomal dominant disease. Am J Hum Genet 1990; 47:904-14.
154. Cormier V, Rotig A, Tardieu M, Colonna M, Saudubray JM, Munnich A. Autosomal dominant deletions of the mitochondrial genome in a case of progressive encephalomyopathy. Am J Hum Genet 1991; 48:643-8.
155. Suomalainen A, Majander A, Haltia M, Somer H, Lonnqvist J, Savontaus ML, et al. Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. J Clin Invest 1992; 90:61-6.
156. Suomalainen A, Kaukonen J, Amati P, Timonen R, Haltia M, Weissenbach J, et al. An autosomal locus predisposing to deletions of mitochondrial DNA. Nat Genet 1995; 9:146-51.
157. Kaukonen JA, Amati P, Suomalainen A, Rotig A, Piscaglia MG, Salvi F, et al. An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p. Am J Hum Genet 1996; 58:763-9.
158. Bardosi A, Creutzfeldt W, DiMauro S, Felgenhauer K, Friede RL, Goebel HH, et al. Myo-, neuro-, gastrointestinal encephalopathy (MNGIE syndrome) due to partial deficiency of cytochrome-c-oxidase. A new mitochondrial multisystem disorder. Acta Neuropathol 1987; 74:248-58.
159. Hirano M, Garcia-de-Yebenes J, Jones AC, Nishino I, DiMauro S, Carlo JR, et al. Mitochondrial neurogastrointestinal encephalomyopathy syndrome maps to chromosome 22q13.32-qter. Am J Hum Genet 1998; 63:526-33.
160. Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 1999; 283:689-92.
161. Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E, et al. mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet 1991; 48:492-501.
162. Tritschler HJ, Andreetta F, Moraes CT, Bonilla E, Arnaudo E, Danon MJ, et al. Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA. Neurology 1992; 42:209-17.
163. Bodnar AG, Cooper JM, Holt IJ, Leonard JV, Schapira AH. Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion. Am J Hum Genet 1993; 53:663-9.
164. Taanman JW, Bodnar AG, Cooper JM, Morris AA, Clayton PT, Leonard JV, et al. Molecular mechanisms in mitochondrial DNA depletion syndrome. Hum Mol Genet 1997; 6:935-42.
165. Lamhonwah AM, Tein I. Carnitine uptake defect: frameshift mutations in the human plasmalemmal carnitine transporter gene. Biochem Biophys Res Commun 1998; 252:396-401.
166. Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999; 21:91-4.
167. Tang NLS, Ganapathy V, Wu X, Hui J, Seth P, Yuen PMP, et al. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet 1999; 8:655-60.
168. Wang Y, Ye J, Ganapathy V, Longo N. Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci USA 1999; 96:2356-60.
169. Engel WK, Vick NA, Glueck CJ, Levy RI. A skeletal-muscle disorder associated with intermittent symptoms and a possible defect of lipid metabolism. N Engl J Med 1970; 282:697-704.
170. DiMauro S, DiMauro PM. Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science 1973; 182:929-31.
171. Falik-Borenstein ZC, Jordan SC, Saudubray JM, Brivet M, Demaugre F, Edmond J, et al. Brief report: renal tubular acidosis in carnitine palmitoyltransferase type 1 deficiency. N Engl J Med 1992; 327:24-7.
172. Taroni F, Verderio E, Fiorucci S, Cavadini P, Finocchiaro G, Uziel G, et al. Molecular characterization of inherited carnitine palmitoyltransferase II deficiency. Proc Natl Acad Sci USA 1992; 89:8429-33.
173. Taroni F, Verderio E, Dworzak F, Willems PJ, Cavadini P, DiDonato S. Identification of a common mutation in the carnitine palmitoyltransferase II gene in familial recurrent myoglobinuria patients. Nat Genet 1993; 4:314-20.
174. Bonnefont JP, Taroni F, Cavadini P, Cepanec C, Brivet M, Saudubray JM, et al. Molecular analysis of carnitine palmitoyltransferase II deficiency with hepatocardiomuscular expression. Am J Hum Genet 1996; 58:971-8.
175. Bougneres PF, Saudubray JM, Marsac C, Bernard O, Odievre M, Girard J. Fasting hypoglycemia resulting from hepatic carnitine palmitoyl transferase deficiency. J Pediatr 1981; 98:742-6.
176. Ijlst L, Mandel H, Oostheim W, Ruiter JP, Gutman A, Wanders RJ. Molecular basis of hepatic carnitine palmitoyltransferase I deficiency. J Clin Invest 1998; 102:527-31.
177. Britton CH, Schultz RA, Zhang B, Esser V, Foster DW, McGarry JD. Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene. Proc Natl Acad Sci U S A 1995; 92:1984-8.
178. Huizing M, Ruitenbeek W, van den Heuvel LP, Dolce V, lacobazzi V, Smeitink JA, et al. Human mitochondrial transmembrane metabolite carriers: tissue distribution and its implication for mitochondrial disorders. J Bioenerg Biomembr 1998; 30:277-84.
179. Matsubara Y, Narisawa K, Miyabayashi S, Tada K, Coates PM, Bachmann C, et al. Identification of a common mutation in patients with medium-chain acyl- CoA dehydrogenase deficiency. Biochem Biophys Res Commun 1990; 171:498-505.
180. Van Hove JL, Zhang W, Kahler SG, Roe CR, Chen YT, Terada N, et al. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood. Am J Hum Genet 1993; 52:958-66.
181. Roe CR, Millington DS, Maltby DA, Kinnebrew P. Recognition of medium-chain acyl-CoA dehydrogenase deficiency in asymptomatic siblings of children dying of sudden infant death or Reye- like syndromes. J Pediatr 1986; 108:13-8.
182. Turnbull DM, Bartlett K, Stevens DL, Alberti KG, Gibson GJ, Johnson MA, et al. Short-chain acyl-CoA dehydrogenase deficiency associated with a lipid- storage myopathy and secondary carnitine deficiency. N Engl J Med 1984; 311:1232-6.
183. Naito E, Indo Y, Tanaka K. Identification of two variant short chain acyl-coenzyme A dehydrogenase alleles, each containing a different point mutation in a patient with short chain acyl-coenzyme A dehydrogenase deficiency. J Clin Invest 1990; 85:1575-82.
184. Hale DE, Batshaw ML, Coates PM, Frerman FE, Goodman SI, Singh I, et al. Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia. Pediatr Res 1985; 19:666-71.
185. Aoyama T, Souri M, Ueno I, Kamijo T, Yamaguchi S, Rhead WJ, et al. Cloning of human very-long-chain acylcoenzyme A dehydrogenase and molecular characterization of its deficiency in two patients. Am J Hum Genet 1995; 57:273-83.
186. Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, et al. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. Am J Hum Genet 1999; 64:479-94.
187. Izai K, Uchida Y, Orii T, Yamamoto S, Hashimoto T. Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. I. Purification and properties of very-long-chain acyl-coenzyme A dehydrogenase. J Biol Chem 1992; 267:1027-33.
188. Ijlst L, Ruiter JP, Hoovers JM, Jakobs ME, Wanders RJ. Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene. J Clin Invest 1996; 98:1028-33.
189. Przyrembel H, Wendel U, Becker K, Bremer HJ, Bruinvis L, Ketting D, et al. Glutaric aciduria type II: report on a previously undescribed metabolic disorder. Clin Chim Acta 1976; 66:227-39.
190. Menkes JH, Hurst PL, Craig JM. A new syndrome: Progressive familial infantile cerebral dysfunction associated with an unusual urinary substance. Pediatrics 1954; 14:462.
191. Chuang DT, Shih VE. Disorders of branched chain amino acid and keto acid metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. 7 ed. New York: McGraw-Hill; 1995: 1239-77.
192. Budd MA, Tanaka K, Holmes LB, Efron ML, Crawford JD, Isselbacher KJ. Isovaleric acidemia. Clinical features of a new genetic defect of leucine metabolism. N Engl J Med 1967; 277:321-7.
193. Mitchell GA, Robert MF, Hruz PW, Wang S, Fontaine G, Behnke CE, et al. 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. J Biol Chem 1993; 268:4376-81.
194. Faull KF, Bolton PD, Halpern B, Hammond J, Danks DM. The urinary organic acid profile associated with 3-hydroxy-3- methylglutaric aciduria. Clin Chim Acta 1976; 73:553-9.
195. Fukao T, Yamaguchi S, Tomatsu S, Orii T, Frauendienst-Egger G, Schrod L, et al. Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency. Biochem Biophys Res Commun 1991; 179:124-9.
196. Daum RS, Lamm PH, Mamer OA, Scriver CR. A "new" disorder of isoleucine catabolism. Lancet 1971; 2:1289-90.
197. Daum RS, Scriver CR, Mamer OA, Delvin E, Lamm P, Goldman H. An inherited disorder of isoleucine catabolism causing accumulation of αa-methylacetoacetate and α-methyl-β-hydroxybutyrate, and intermittent metabolic acidosis. Pediatr Res 1973; 7:149-60.
198. Gompertz D, Storrs CN, Bau DC, Peters TJ, Hughes EA. Localisation of enzymic defect in propionicacidaemia. Lancet 1970; 1:1140-3.
199. Richard E, Desviat LR, Perez B, Perez-Cerda C, Ugarte M. Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients. Hum Genet 1997; 101:93-6.
200. Suzuki Y, Aoki Y, Ishida Y, Chiba Y, Iwamatsu A, Kishino T, et al. Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. Nat Genet 1994; 8:122-8.
201. Rosenberg LE, Lilljeqvist AC, Hsia YE. Methylmalonic aciduria. An inborn error leading to metabolic acidosis, long-chain ketonuria and intermittent hyperglycinemia. N Engl J Med 1968; 278:1319-22.
202. Rosenberg LE, Lilljeqvist A, Hsia YE. Methylmalonic aciduria: metabolic block localization and vitamin B 12 dependency. Science 1968; 162:805-7.
203. Fenton WA, Hack AM, Kraus JP, Rosenberg LE. Immunochemical studies of fibroblasts from patients with methylmalonyl- CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import. Proc Natl Acad Sci USA 1987; 84:1421-4.
204. Mudd SH, Levy HL, Abeles RH, Jennedy JP, Jr. A derangement in B 12 metabolism leading to homocystinemia, cystathioninemia and methylmalonic aciduria. Biochem Biophys Res Commun 1969; 35:121-6.
205. Goodman SI, Markey SP, Moe PG, Miles BS, Teng CC. Glutaric aciduria; a "new" disorder of amino acid metabolism. Biochem Med 1975; 12:12-21.
206. Schagger H. Electrophoretic techniques for isolation and quantification of oxidative phosphorylation complexes from human tissues. Methods Enzymol 1996; 264:555-66.
207. Fields S, Kohara Y, Lockhart DJ. Functional genomics. Proc Natl Acad Sci USA 1999; 96:8825-6.