Current Opinion on the Clinical Approach to the Diagnosis of Mitochondrial Disease
Article Outline
SUMMARY
Knowing the molecular basis of mitochondria, the aging process of the mitochondrial machinery and recognition of its disorders are becoming more important in modern medicine. The diagnosis of mitochondrial disease (MtD) is possible only when one is aware of it. The heterogeneity of MtD in terms of its phenotype expression and genotype variations makes MtD very unique. Current opinion on the clinical approach to patients with suspected mitochondrial disorders are highlighted in this review.
Key Words: aging , mitochondrial disease , mitochondrial DNA , mutation , nuclear DNA , oxidative phosphorylation
No full text is available. To read the body of this article, please view the PDF online.
References
- . Intramitochondrial fibers with DNA characteristics. I. Fixation and electron staining reactions . J Cell Biol . 1963;19:593–611
- Sequence and organization of human mitochondrial genome . Nature . 1981;290:457–465
- . Mitochondrial encephalomyopathies: a group of neuromuscular disorders with defects in oxidative metabolism . Isr J Med Sci . 1977;13:161–164
- . Oxidative phosphorylation diseases. Disorders of two genomes . In: Harris H , Hirschhorn K editor. Advances in Human Genetics . New York: Plenum; 1970;p. 267–330 19
- . Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies . Nature . 1988;331:717–719
- . Metabolic myopathies . In: Rowland LP , DiMauro S editor. Myopathies, Handbook of Clinical Neurology . Amsterdam: Elsevier Science Publishers B.V.; 1992;p. 496–497 18
- . Mitochondrial diseases . In: Engel AG , Franzini-Armstrong C editor. 2 nd edition. Myology . vol. 2: New York: McGraw-Hill; 1994;p. 1622–1623
- . A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study . J Clin Invest . 1962;41:1776–1804
- . The expanding phenotype of mitochondrial myopathy . Curr Opin Neurol . 2005;18:538–542
- . Mitochondrial myopathy with a defect of mitochondrial protein transport . N Engl J Med . 1990;323:37–42
- . Genotypephenotype correlation of maternally inherited disorders due to mutations in mitochondrial DNA . Taiwan J Obstet Gynecol . 2006;45:201–207
- Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome . N Engl J Med . 1989;320:1293–1299
- . Mitochondria and neuroophthalmologic diseases . In: Scriver CR , Beaudet AL , Sly WS , Valle D editor. The Metabolic and Molecular Basis of Inherited Disease . 8 th edition. New York: McGraw-Hill; 2001;p. 2425–2509 2
- MELAS syndrome: correlation between clinical features and molecular genetic analysis . Acta Neurol Scand . 1994;90:354–359
- . Phenotypic heterogeneity in a Chinese family with mitochondrial disease and A3243G mutation of mitochondrial DNA . Chin Med J (Taipei) . 2000;63:71–76
- . The mitochondrial DNA transfer RNALeu(UUR) A to G(3243) mutation. A clinical and genetic study . Brain . 1995;118:721–734
- . The neurology of mitochondrial DNA disease . Lancet Neurol . 2002;1:343–351
- . Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy . Proc Natl Acad Sci USA . 1989;86:7952–7956
- . Retinitis pigmentosa, external ophthalmoplegia and complete heart block . Ophthalmology . 1958;60:280–289
- . Oxidative phosphorylation diseases . In: Scriver CR , Beaudet AL , Sly WS , Valle D editor. The Metabolic and Molecular Basis of Inherited Disease . New York: McGraw-Hill; 1995;p. 1535–1609
- A new mitochondrial point mutation in the transfer RNA(Leu) gene in a patient with a clinical phenotype resembling Kearns-Sayre syndrome . Arch Neurol . 2001;58:1113–1118
- . White matter involvement in mitochondrial diseases . Mol Genet Metab . 2005;84:127–136
- . Mitochondrial DNA deletion in a girl with manifestations of Kearns-Sayre and Lowe syndromes: an example of phenotypic mimicry? . Am J Med Genet . 1991;41:301–305
- mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial disease . Am J Hum Genet . 1991;48:492–501
- . Mitochondrial encephalomyopathies: gene mutation . Neuromuscul Disord . 2004;14:107–116
- . Leber hereditary optic neuropathy . J Med Genet . 2002;39:162–169
- . White matter abnormalities in Leber's hereditary optic neuropathy due to the 3460 mitochondrial DNA mutation . Eur J Paediatr Neurol . 2002;6:121–123
- . Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distinctive clinical syndrome . Ann Neurol . 1984;16:481–488
- MELAS: clinical features, biochemistry, and molecular genetics . Ann Neurol . 1992;31:391–398
- . Cerebral lactic acidosis correlates with neurological impairment in MELAS . Neurology . 2004;63:2458
- . Koshevnikov syndrome in a patient with MELAS plus syndrome: electron microscopic and neuroimage studies . Chin Med J (Beijing) . 1997;110:726–730
- . Basal ganglia calcification in mitochondrial disorders . Metab Brain Dis . 2005;20:219–226
- . Deep white matter pathologic features in watershed regions: a novel pattern of central nervous system involvement in MELAS . Arch Neurol . 2005;62:1154–1156
- Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT . Neuroradiology . 2000;42:26–29
- . Brain SPECT studies in patients with A3243G mutation of the mitochondrial DNA . Ann NY Acad Sci . 2005;1042:48–54
- . Increased mitochondrial DNA in blood vessels and ragged-red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) . Ann Neurol . 1993;33:275–280
- . A mutation in the tRNA (Leu) (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies . Nature . 1990;348:651–653
- Widespread tissue distribution of a tRNALeu(UUR) mutation in the mitochondrial DNA of a patient with MELAS syndrome . Neurology . 1991;41:1663–1664
- . Variable distribution of mutant mitochondrial DNAs tRNA(Leu[3243]) in tissues of symptomatic relatives with MELAS: the role of mitotic segregation . Neurology . 1993;43:1586–1590
- . Ophthalmologic manifestations in MELAS syndrome . Arch Neurol . 1993;50:977–980
- . Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes . Brain . 1997;120:1713–1721
- . The study of A3243G and G13513A mitochondria DNA point mutation in patients with cerebral infarction . Chin Med J (Beijing) . 2001;114:129–135
- . MELAS with point mutations involving tRNALeu (A3243G) and tRNAGlu (14693G) . Muscle Nerve . 2003;28:575–581
- Phenotypic heterogeneity in families with the myoclonic epilepsy and ragged-red fiber disease point mutation in mitochondrial DNA . Ann Neurol . 1993;33:640–645
- Clinical features associated with the A→G transition at nucleotide 8344 of mtDNA (“MERRF mutation”) . Neurology . 1993;43:1200–1206
- Uniform tissue distribution of tRNA(Lys) mutation in mitochondrial DNA in MERRF patients . Neurology . 1993;43:1198–1200
- . Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA Lys mutation . Cell . 1990;61:931–937
- Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA(Leu)(UUR) . Lancet . 1991;338:143–147
- Oculopharyngeal somatic myopathy in a patient with a novel large-scale 3399bp deletion and a homoplasmic T5814C transition of the mitochondrial DNA . Clin Neurol Neurosurg . 2006;108:407–410
- The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants . Hum Mol Genet . 2004;13:869–879
- The mitochondrial DNA G13513A transition in ND5 is associated with LHON/MELAS overlap syndrome and may be a frequent cause of MELAS . Ann Neurol . 1999;46:916–919
- . Sporadic MERRF/MELAS overlap syndrome associated with the 3243 tRNA(Leu(UUR)) mutation of mitochondrial DNA . Muscle Nerve . 1996;19:187–190
- CPEO and carnitine deficiency overlapping in MELAS syndrome . Acta Neurol Scand . 1995;92:252–255
- Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder . Neurology . 1994;44:721–727
- Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation . J Neurol . 2005;252:655–662
- Multiple mtDNA deletions with features of MNGIE . Neurology . 2002;59:926–929
- . Mitochondrial genes in degenerative diseases, cancer and aging . In: Rimon DL , Connor JM , Pyeritz RE , Korf BR editor. Emery and Rimons's Principles and Practice of Medical Genetics . 4 th edition. London: Churchill Livingstone; 2002;p. 299–409 1
- The mitochondrial DNA transfer RNA (Lys) A to G (3243) mutation and the syndrome of myoclonic epilepsy with ragged-red fibers (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA . Brain . 1993;116:617–632
- Quantitation of heteroplasmy of mitochondrial tRNA(Leu(UUR)) gene using PCR-SSCP . Muscle Nerve . 1995;18:1390–1397
- The mutant mitochondrial genes in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were selectively amplified through generations . J Inherit Metab Dis . 1992;15:803–808
- . Roles for imaging in understanding the pathophysiology, clinical evaluation, and management of patients with mitochondrial disease . J Neuroimaging . 2003;13:293–302
- . Rapid examination of muscle tissue: an improved trichrome method for freshfrozen biopsy sections . Neurology . 1963;13:919–923
- . Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy . Proc Natl Acad Sci USA . 1989;86:2379–2382
- Coenzyme Q-responsive Leigh's encephalopathy in two sisters . Ann Neurol . 2002;52:750–754
- . Mitochondrial myopathy caused by long-term zidovudine therapy . N Engl J Med . 1990;322:1098–1105
- . Mitochondrial changes in ischemic skeletal muscle . J Ultrastruct Res . 1977;60:121–133
- . Human myopathy with giant abnormal mitochondria . Science . 1964;145:493–496
- . Two childhood myopathies with abnormal mitochondria: I. Megoconial myopathy. II. Pleoconial myopathy . Brain . 1966;89:133–158
- . Electron cytochemistry of crystalline inclusions in human skeletal muscle mitochondria . J Ultrastruct Res . 1975;51:404–408
PII: S1873-9598(08)70020-6
doi:10.1016/S1873-9598(08)70020-6
© 2007 Elsevier B.V. All rights reserved.
