Hostname: page-component-848d4c4894-xm8r8 Total loading time: 0 Render date: 2024-06-17T03:31:28.468Z Has data issue: false hasContentIssue false
  • English
  • Français

Mitochondrial Ataxias

Published online by Cambridge University Press:  02 December 2014

Josef Finsterer
Josef Finsterer*
Affiliation:
Krankenanstalt Rudolfstiftung, Vienna, Austria, Europe
*
Postfach 20, 1180 Vienna, Austria, Europe
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Mitochondrial disorders (MIDs) are an increasingly recognized condition. The second most frequently affected organ in MIDs is the central nervous system. One of the most prevalent clinical CNS manifestations of MIDs is ataxia. Ataxia may be even the dominant manifestation of a MID. This is why certain MIDs should be included in the classification of heredoataxias or at least considered as differentials of classical heredoataxias. MIDs due to mutations of the mitochondrial DNA, which develop ataxia include the MERRF, NARP, MILS, or KSS syndrome. More rarely, ataxia may be a feature of MELAS, LHON, PS, MIDD, or MSL. MIDs due to mutations of the nuclear DNA, which develop ataxia include LS, SANDO, SCAE, AHS, XSLA/A, IOSCA, MIRAS, MEMSA, or LBSL syndrome. More rarely ataxia can be found in AD-CPEO, AR-CPEO, MNGIE, DIDMOAD, CoQ-deficiency, ADOAD, DCMA, or PDC-deficiency. MIDs most frequently associated with ataxia are the non-syndromic MIDs. Syndromic and non-syndromic MIDs with ataxia should be delineated from classical heredoataxias to initiate appropriate symptomatic or supportive treatment.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 36 , Issue 5 , September 2009 , pp. 543 - 553
Copyright
Copyright © The Canadian Journal of Neurological 2009

References

1.DiMauro, S, Schon, EA.Mitochondrial disorders in the nervous system. Annu Rev Neurosci. 2008;31:91–123.CrossRefGoogle ScholarPubMed
2.Zeviani, M, Di Donato, S.Mitochondrial disorders. Brain. 2004;127: 2153–72.CrossRefGoogle ScholarPubMed
3.Montirosso, R, Brambilla, D, Felisari, G, Sclaunich, F, Filipponi, E, Pozzoli, U, et al.Electrophysiological analysis of cognitive slowing in subjects with mitochondrial encephalomyopathy. J Neurol Sci. 2002;194:3–9.CrossRefGoogle ScholarPubMed
4.Finsterer, J.Overview on visceral manifestations of mitochondrial disorders. Neth J Med. 2006;64:61–71.Google ScholarPubMed
5.Wong, LJ, Naviaux, RK, Brunetti-Pierri, N, Zhang, Q, Schmitt, ES, Truong, C, et al.Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Hum Mutat. 2008;29:E150–72.CrossRefGoogle ScholarPubMed
6.Finsterer, J. Ataxias with autosomal, X-chromosomal, or maternal inheritance. J Neurol Sci. 2009; In press 2009.CrossRefGoogle Scholar
7.Orr, HT, Zoghbi, HY.Trinucleotide repeat disorders. Annu Rev Neurosci. 2007;30:575–621.CrossRefGoogle ScholarPubMed
8.Schaefer, AM, McFarland, R, Blakely, EL, He, L, Whittaker, RG, Taylor, RW, et al.Prevalence of mitochondrial DNA disease in adults. Ann Neurol. 2008;63:35–9.Google Scholar
9.Chan, SS, Longley, MJ, Copeland, WC.The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit. J Biol Chem. 2005;280:31341–6.CrossRefGoogle ScholarPubMed
10.Finsterer, J, Harbo, HF, Baets, J, van Broeckhoven, C, Di Donato, S, Fontaine, B, et al. EFNS guidelines for the molecular diagnosis of neurogenetic disorders (II). Mitochondrial disorders and dementia. Eur J Neurol. 2009;In press 2009.Google Scholar
11.Lindberg, C, Moslemi, AR, Oldfors, A.MELAS syndrome in a patient with a point mutation in MTTS1. Acta Neurol Scand. 2008;117:128–32.Google Scholar
12.Petruzzella, V, Zoccolella, S, Amati, A, Torraco, A, Lamberti, P, Carnicella, F, et al.Cerebellar ataxia as atypical manifestation of the 3243A>G MELAS mutation. Clin Genet. 2004;65:64–5.CrossRefGoogle ScholarPubMed
13.Teive, HA, Munhoz, RP, Muzzio, JA, Scola, RH, Kay, CK, Raskin, S, et al.Cerebellar ataxia, myoclonus, cervical lipomas, and MERRF syndrome. Case report. Mov Disord. 2008;23:1191–2.CrossRefGoogle ScholarPubMed
14.Ito, S, Shirai, W, Asahina, M, Hattori, T.Clinical and brain MR imaging features focusing on the brain stem and cerebellum in patients with myoclonic epilepsy with ragged-red fibers due to mitochondrial A8344G mutation. Am J Neuroradiol. 2008;29:392–5.CrossRefGoogle ScholarPubMed
15.Orcesi, S, Gorni, K, Termine, C, Uggetti, C, Veggiotti, P, Carrara, F, et al.Bilateral putaminal necrosis associated with the mitochondrial DNA A8344G myoclonus epilepsy with ragged red fibers (MERRF) mutation: an infantile case. J Child Neurol. 2006;21:79–82.Google Scholar
16.Fukuhara, N.Fukuhara disease. Brain Nerve. 2008;60:53–8.Google Scholar
17.Horvath, R, Kley, RA, Lochmüller, H, Vorgerd, M.Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNALys. Neurology. 2007;68:56–8.Google Scholar
18.Funakawa, I, Kato, H, Terao, A, Ichihashi, K, Kawashima, S, Hayashi, T, et al.Cerebellar ataxia in patients with Leber’s hereditary optic neuropathy. J Neurol. 1995;242:75–7.Google Scholar
19.Murakami, T, Mita, S, Tokunaga, M, Maeda, H, Ueyama, H, Kumamoto, T, et al.Hereditary cerebellar ataxia with Leber’s hereditary optic neuropathy mitochondrial DNA 11778 mutation. J Neurol Sci. 1996;142:111–3.CrossRefGoogle ScholarPubMed
20.Man, PY, Turnbull, DM, Chinnery, PF.Leber hereditary optic neuropathy. J Med Genet. 2002;39:162–9.Google Scholar
21.Debray, FG, Lambert, M, Lortie, A, Vanasse, M, Mitchell, GA.Longterm outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation. Am J Med Genet. 2007;143A: 2046–51.Google Scholar
22.Tsao, CY, Mendell, JR, Bartholomew, D.High mitochondrial DNA T8993G mutation (90%) without typical features of Leigh’s and NARP syndromes. J Child Neurol. 2001;16:533–5.Google Scholar
23.Mitani, M, Jinnai, K, Takahashi, K, Koide, R, Tsuji, S.A case of NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) with a T-to-C point mutation at nt 8993 of mitochondrial DNA. Clin Neurol. 2000;40:600–4.Google Scholar
24.Rojo, A, Campos, Y, Sánchez, JM, Bonaventura, I, Aguilar, M, García, A, et al.NARP-MILS syndrome caused by 8993 T>G mitochondrial DNA mutation: a clinical, genetic and neuropathological study. Acta Neuropathol. 2006;111:610–16.Google Scholar
25.Uziel, G, Moroni, I, Lamantea, E, Fratta, GM, Ciceri, E, Carrara, F, et al.Mitochondrial disease associated with the T8993G mutation of the mitochondrial ATPase 6 gene: a clinical, biochemical, and molecular study in six families. J Neurol Neurosurg Psychiatry. 1997;63:16–22.CrossRefGoogle ScholarPubMed
26.Childs, AM, Hutchin, T, Pysden, K, Highet, L, Bamford, J, Livingston, J, et al.Variable phenotype including Leigh syndrome with a 9185T>C mutation in the MTATP6 gene. Neuropediatrics. 2007;38:313–6.Google Scholar
27.Castagna, AE, Addis, J, McInnes, RR, Clarke, JT, Ashby, P, Blaser, S, et al.Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA. Am J Med Genet. 2007;143A: 808–16.CrossRefGoogle Scholar
28.Campos, Y, Martin, MA, Rubio, JC, Solana, LG, García-Benayas, C, Terradas, JL, et al.Leigh syndrome associated with the T9176C mutation in the ATPase6 gene of mitochondrial DNA. Neurology. 1997;49:595–7.Google Scholar
29.Finsterer, J.Leigh and Leigh-like syndrome in children and adults. Pediat Neurol. 2008;39:223–35.Google Scholar
30.Santorelli, FM, Shanske, S, Macaya, A, DeVivo, DC, DiMauro, S.The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh’s syndrome. Ann Neurol. 1993;34:827–34.Google Scholar
31.Lee, HF, Lee, HJ, Chi, CS, Tsai, CR, Chang, TK, Wang, CJ.The neurological evolution of Pearson syndrome: case report and literature review. Eur J Paediatr Neurol. 2007;11:208–14.CrossRefGoogle ScholarPubMed
32.McShane, MA, Hammans, SR, Sweeney, M, Holt, IJ, Beattie, TJ, Brett, EM, et al.Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. Am J Hum Genet. 1991;48:39–42.Google Scholar
33.Riera, AR, Kaiser, E, Levine, P, Schapachnik, E, Dubner, S, Ferreira, C, et al.Kearns-Sayre syndrome: electro-vectorcardiographic evolution for left septal fascicular block of the his bundle. J Electrocardiol. 2008;41:675–8.CrossRefGoogle ScholarPubMed
34.Zoccolella, S, Torraco, A, Amati, A, Lamberti, P, Serlenga, L, Papa, S, et al.Unusual clinical presentation of a patient carrying a novel single 1.8 kb deletion of mitochondrial DNA. Funct Neurol. 2006;21:39–41.Google Scholar
35.Hourani, RG, Barada, WM, Al-Kutoubi, AM, Hourani, MH.Atypical MRI findings in Kearns-Sayre syndrome: T2 radial stripes. Neuropediatrics. 2006;37:110–13.Google Scholar
36.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.CrossRefGoogle Scholar
37.Van den Ouweland, JM, Lemkes, HH, Gerbitz, KD, Maassen, JA, et al.Maternally inherited diabetes and deafness (MIDD): a distinct subtype of diabetes associated with a mitochondrial tRNA(Leu)(UUR) gene point mutation. Muscle Nerve. 1995;3:S124–30.CrossRefGoogle ScholarPubMed
38.Chen, YN, Liou, CW, Huang, CC, Lin, TK, Wei, YH.Maternally inherited diabetes and deafness (MIDD) syndrome: a clinical and molecular genetic study of a Taiwanese family. Chang Gung Med J. 2004;27:66–73.Google ScholarPubMed
39.Kobayashi, Z, Tsunemi, T, Miake, H, Tanaka, S, Watabiki, S, Morokuma, Y.A mother and a child with maternally inherited diabetes and deafness (MIDD) showing atrophy of the cerebrum, cerebellum and brainstem on magnetic resonance imaging (MRI). Intern Med. 2005;44:328–31.Google Scholar
40.Naumann, M, Kiefer, R, Toyka, KV, Sommer, C, Seibel, P, Reichmann, H.Mitochondrial dysfunction with myoclonus epilepsy and ragged-red fibers point mutation in nerve, muscle, and adipose tissue of a patient with multiple symmetric lipomatosis. Muscle Nerve. 1997;20:833–9.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
41.Corona, P, Lamantea, E, Greco, M, Carrara, F, Agostino, A, Guidetti, D, et al.Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. Ann Neurol. 2002;51:118–22.CrossRefGoogle Scholar
42.Casali, C, Fabrizi, GM, Santorelli, FM, Colazza, G, Villanova, M, Dotti, MT, et al.Mitochondrial G8363A mutation presenting as cerebellar ataxia and lipomas in an Italian family. Neurology. 1999;52:1103–4.CrossRefGoogle Scholar
43.Pancrudo, J, Shanske, S, Bonilla, E, Daras, M, Akman, HO, Krishna, S, et al.Mitochondrial encephalomyopathy due to a novel mutation in the tRNAGlu of mitochondrial DNA. J Child Neurol. 2007;22:858–62.CrossRefGoogle ScholarPubMed
44.Zeviani, M, Bertagnolio, B, Uziel, G.Neurological presentations of mitochondrial diseases. J Inherit Metab Dis. 1996;19:504–20.Google Scholar
45.Salviati, L, Freehauf, C, Sacconi, S, DiMauro, S, Thoma, J, Tsai, AC.Novel SURF1 mutation in a child with subacute encephalopathy and without the radiological features of Leigh Syndrome. Am J Med Genet. 2004;128A: 195–8.Google Scholar
46.Kawai, H, Akaike, M, Yokoi, K, Nishida, Y, Kunishige, M, Mine, H, et al.Mitochondrial encephalomyopathy with autosomal dominant inheritance: a clinical and genetic entity of mitochondrial diseases. Muscle Nerve. 1995;18:753–60.Google Scholar
47.Spinazzola, A, Viscomi, C, Fernandez-Vizarra, E, Carrara, F, D’Adamo, P, Calvo, S, et al.MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat Genet. 2006;38:570–5.Google Scholar
48.Mancuso, M, Filosto, M, Bellan, M, Liguori, R, Montagna, P, Baruzzi, A, et al.POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness. Neurology. 2004;62:316–8.CrossRefGoogle ScholarPubMed
49.Gago, MF, Rosas, MJ, Guimarães, J, Ferreira, M, Vilarinho, L, Castro, L, et al.SANDO: two novel mutations in POLG1 gene. Neuromuscul Disord. 2006;16:507–9.Google Scholar
50.Milone, M, Brunetti-Pierri, N, Tang, LY, Kumar, N, Mezei, MM, Josephs, K, et al.Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations. Neuromuscul Disord. 2008;18:626–32.Google Scholar
51.Hudson, G, Deschauer, M, Busse, K, Zierz, S, Chinnery, PF.Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism. Neurology. 2005;64:371–3.CrossRefGoogle ScholarPubMed
52.Galassi, G, Lamantea, E, Invernizzi, F, Tavani, F, Pisano, I, Ferrero, I, et al.Additive effects of POLG1 and ANT1 mutations in a complex encephalomyopathy. Neuromuscul Disord. 2008;18:465–70.Google Scholar
53.Gordon, N.Alpers syndrome: progressive neuronal degeneration of children with liver disease. Dev Med Child Neurol. 2006;48:1001–3.CrossRefGoogle ScholarPubMed
54.Naviaux, RK, Nyhan, WL, Barshop, BA, Poulton, J, Markusic, D, Karpinski, NC, et al.Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers’ syndrome. Ann Neurol. 1999;45:54–8.Google Scholar
55.Kollberg, G, Moslemi, AR, Darin, N, Nennesmo, I, Bjarnadottir, I, Uvebrant, P, et al.POLG1 mutations associated with progressive encephalopathy in childhood. J Neuropathol Exp Neurol. 2006;65:758–68.Google Scholar
56.Davidzon, G, Mancuso, M, Ferraris, S, Quinzii, C, Hirano, M, Peters, HL, et al.POLG mutations and Alpers syndrome. Ann Neurol. 2005;57:921–3.Google Scholar
57.Hakonen, AH, Isohanni, P, Paetau, A, Herva, R, Suomalainen, A, Lönnqvist, T.Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain. 2007;130:3032–40.Google Scholar
58.Debouverie, M, Wagner, M, Ducrocq, X, Grignon, Y, Mousson, B, Weber, M.MNGIE syndrome in 2 siblings. Rev Neurol (Paris). 1997;153:547–53.Google ScholarPubMed
59.DiMauro, S, Schon, EA.Mitochondrial respiratory-chain diseases. N Engl J Med. 2003;348:2656–68.Google Scholar
60.Nishigaki, Y, Marti, R, Hirano, M.ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy. Hum Mol Genet. 2004; 13:91–101.Google Scholar
61.Marti, R, Spinazzola, A, Tadesse, S, Nishino, I, Nishigaki, Y, Hirano, M.Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays. Clin Chem. 2004; 50:120–4.Google Scholar
62.Gillis, L, Kaye, E.Diagnosis and management of mitochondrial diseases. Pediatr Clin N Am. 2002;49:203–19.Google Scholar
63.Allikmets, R, Raskind, WH, Hutchinson, A, Schueck, ND, Dean, M, Koeller, DM.Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum Mol Genet. 1999;8:743–9.Google Scholar
64.Pondarre, C, Campagna, DR, Antiochos, B, Sikorski, L, Mulhern, H, Fleming, MD.Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. Blood. 2007;109:3567–9.CrossRefGoogle ScholarPubMed
65.Hellier, KD, Hatchwell, E, Duncombe, AS, Kew, J, Hammans, SR.X-linked sideroblastic anaemia with ataxia: another mitochondrial disease? J Neurol Neurosurg Psychiatry. 2001;70:65–9.Google Scholar
66.Maguire, A, Hellier, K, Hammans, S, May, A.X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L. Br J Haematol. 2001;115:910–17.Google Scholar
67.Amati-Bonneau, P, Valentino, ML, Reynier, P, Gallardo, ME, Bornstein, B, Boissière, A, et al.OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes. Brain. 2008;131:338–51.Google Scholar
68.Hudson, G, Amati-Bonneau, P, Blakely, EL, Stewart, JD, He, L, Schaefer, AM, et al.Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain. 2008;131:329–37.Google Scholar
69.Liguori, M, La Russa, A, Manna, I, Andreoli, V, Caracciolo, M, Spadafora, P, et al.A phenotypic variation of dominant optic atrophy and deafness (ADOAD) due to a novel OPA1 mutation. J Neurol. 2008;255:127–9.Google Scholar
70.Lönnqvist, T, Paetau, A, Nikali, K, von Boguslawski, K, Pihko, H.Infantile onset spinocerebellar ataxia with sensory neuropathy (IOSCA): neuropathological features. J Neurol Sci. 1998;161:57–65.Google Scholar
71.Nikali, K, Suomalainen, A, Saharinen, J, Kuokkanen, M, Spelbrink, JN, Lönnqvist, T, et al.Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. Hum Mol Genet. 2005;14:2981–90.Google Scholar
72.Hakonen, AH, Goffart, S, Marjavaara, S, Paetau, A, Cooper, H, Mattila, K, et al.Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion. Hum Mol Genet. 2008;17:3822–35.Google Scholar
73.Goffart, S, Cooper, HM, Tyynismaa, H, Wanrooij, S, Suomalainen, A, Spelbrink, JN.Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. Hum Mol Genet. 2009;18:328–40.Google Scholar
74.Rantamäki, M, Luoma, P, Virta, JJ, Rinne, JO, Paetau, A, Suomalainen, A, et al.Do carriers of POLG mutation W748S have disease manifestations? Clin Genet. 2007;72:532–7.CrossRefGoogle ScholarPubMed
75.Hakonen, AH, Heiskanen, S, Juvonen, V, Lappalainen, I, Luoma, PT, Rantamaki, M, et al.Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet. 2005;77:430–41.Google Scholar
76.Scheper, GC, van der Klok, T, van Andel, RJ, van Berkel, CG, Sissler, M, Smet, J, et al.Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet. 2007;39:534–9.Google Scholar
77.Medlej, R, Wasson, J, Baz, P, Azar, S, Salti, I, Loiselet, J, et al.Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. J Clin Endocrinol Metab. 2004;89: 1656–61.CrossRefGoogle ScholarPubMed
78.Barrett, TG, Bundey, SE, Macleod, AF.Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet. 1995;346:1458–63.Google Scholar
79.Ajlouni, K, Jarrah, N, El-Khateeb, M, El-Zaheri, M, El Shanti, H, Lidral, A, et al.Wolfram syndrome: identification of a phenotypic and genotypic variant from Jordan. Am J Med Genet. 2002;115:61–5.Google Scholar
80.Cryns, K, Sivakumaran, TA, Van den Ouweland, JM, Pennings, RJ, Cremers, CW, Flothmann, K, et al.Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. Hum Mutat. 2003;22:275–87.Google Scholar
81.Barrientos, A, Casademont, J, Saiz, A, Cardellach, F, Volpini, V, Solans, A, et al.Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion. Am J Hum Genet. 1996;58:963–70.Google Scholar
82.Montero, R, Pineda, M, Aracil, A, Vilaseca, MA, Briones, P, Sánchez-Alcázar, JA, et al.Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10 deficiency. Cerebellum. 2007;6:118–22.CrossRefGoogle ScholarPubMed
83.Leshinsky-Silver, E, Levine, A, Nissenkorn, A, Barash, V, Perach, M, Buzhaker, E, et al.Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency. Mol Genet Metab. 2003;79:288–93.Google Scholar
84.Debray, FG, Lambert, M, Gagne, R, Maranda, B, Laframboise, R, MacKay, N, et al.Pyruvate dehydrogenase deficiency presenting as intermittent isolated acute ataxia. Neuropediatrics. 2008;39:20–3.Google Scholar
85.Okajima, K, Korotchkina, LG, Prasad, C, Rupar, T, Phillips, JA 3rd, Ficicioglu, C, et al.Mutations of the E1beta subunit gene (PDHB) in four families with pyruvate dehydrogenase deficiency. Mol Genet Metab. 2008;93:371–80.Google Scholar
86.Davey, KM, Parboosingh, JS, McLeod, DR, Chan, A, Casey, R, Ferreira, P, et al.Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndromelike condition. J Med Genet. 2006;43:385–93.Google Scholar
87.Lodi, R, Rajagopalan, B, Bradley, JL, Taylor, DJ, Crilley, JG, Hart, PE, et al.Mitochondrial dysfunction in Friedreich’s ataxia: from pathogenesis to treatment perspectives. Free Radic Res. 2002;36:461–6.Google Scholar
88.Spacey, SD, Szczygielski, BI, Young, SP, Hukin, J, Selby, K, Snutch, TP.Malaysian siblings with Friedreich ataxia and chorea: a novel deletion in the frataxin gene. Can J Neurol Sci. 2004;31:383–6.Google Scholar
89.Samad, FU, Engel, E, Hartmann, RC.Hypoplastic anemia, Friedreich’s ataxia and chromosomal breakage: case report and review of similar disorders. South Med J. 1973;66:135–40.Google Scholar
90.Campanella, A, Isaya, G, O’Neill, HA, Santambrogio, P, Cozzi, A, Arosio, P, et al.The expression of human mitochondrial ferritin rescues respiratory function in frataxin-deficient yeast. Hum Mol Genet. 2004;13:2279–88.Google Scholar
91.Parini, R, Furlan, F, Notarangelo, L, Spinazzola, A, Uziel, G, Strisciuglio, P, et al.Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients. J Hepatol. 2009;50:215–21.CrossRefGoogle ScholarPubMed
92.Van Goethem, G, Luoma, P, Rantamaki, M, Al Memar, A, Kaakkola, S, Hackman, P, et al.POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology. 2004;63:1251–7.Google Scholar
93.Craig, K, Elliott, HR, Keers, SM, Lambert, C, Pyle, A, Graves, TD, et al.Episodic ataxia and hemiplegia caused by the 8993T->C mitochondrial DNA mutation. J Med Genet. 2007;44:797–9.Google Scholar
94.Laugel, V, This-Bernd, V, Cormier-Daire, V, Speeg-Schatz, C, de Saint-Martin, A, Fischbach, M.Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations. Pediatr Neurol. 2007;36:54–7.Google Scholar
95.Oldfors, A, Holme, E, Tulinius, M, Larsson, NG.Tissue distribution and disease manifestations of the tRNA(Lys) A->G(8344) mitochondrial DNA mutation in a case of myoclonus epilepsy and ragged red fibres. Acta Neuropathol. 1995;90:328–33.Google Scholar
96.Moslemi, AR, Darin, N, Tulinius, M, Oldfors, A, Holme, E.Two new mutations in the MTATP6 gene associated with Leigh syndrome. Neuropediatrics. 2005;36:314–18.CrossRefGoogle ScholarPubMed