Mitochondrial DNA depletion in Leigh syndrome

• Published in: Pediatric neurology 2002-03, Vol.26 (3), p.239-242
• Main Authors: Filiano, James J, Goldenthal, Michael J, Mamourian, Alexander C, Hall, Cara C, Marı́n-Garcı́a, José
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Brain - pathology; DNA, Mitochondrial - metabolism; Electron Transport Complex I; Electron Transport Complex III - metabolism; Errors of metabolism; Humans; Infant, Newborn; Leigh Disease - diagnosis; Leigh Disease - genetics; Leigh Disease - metabolism; Leigh Disease - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mitochondria, Muscle - enzymology; Muscle, Skeletal - metabolism; NADH, NADPH Oxidoreductases - metabolism
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/S0887-8994(01)00377-0

Leigh syndrome is a heterogenous neurologic disease characterized by seizures, developmental delay, muscle weakness, respiratory abnormalities, optic abnormalities, including atrophy and ophthalmoplegia, and progressive cranial nerve degeneration with early onset in infants and children. Diagnosis can be confirmed by characteristic pathologic findings of necrosis in the basal ganglia, thalamus, and brainstem. Severe dysfunction of mitochondrial energy metabolism is generally present and involved in the etiology of this degenerative central nervous system disease. At the molecular level, a number of point mutations have been located in mitochondrial DNA genes, including ATPase6 and tRNA Lys genes, and in nuclear genes encoding subunits of oxidative enzymes, such as pyruvate dehydrogenase. Biochemically these mutations are responsible for enzymatic defects in either respiratory complexes (I, IV, or V) or pyruvate dehydrogenase. We describe here the first case of Leigh syndrome with marked depletion of mitochondrial DNA levels in skeletal muscle and abnormal activities in skeletal muscle of mitochondrial respiratory complexes I, III, IV, and V.