PURPOSE: Leigh syndrome is a subacute neurodegenerative disorder of infancy or early childhood characterized by variable clinical manifestations and characteristic pathologic findings on brain. The characteristic radiological findings revealed bilateral symmetrical high signal intensity in T2-weighted brain MRI imaging. The previous studies reported defects of enzymes involved in aerobic energy metabolism or point mutations in mitochondrial deoxyribonucleic acid(mtDNA), including a T-to-C or T-to-G mutation at nucleotide position(nt) 8993 or 9176 located in adenosinetriphosphatase(ATPase) 6 gene of mtDNA. Therefore, we studied the characteristic clinical, radiological, and genetical findings of Leigh syndrome, diagnosed at the Department of Pediatrics, Asan Medical Center. METHODS: From August 1992 to June 2000, 17 patients were included in this study, who presented charateristic MRI findings of Leigh syndrome. We examined the concentrations of lactate and pyruvate in blood and cerebrospinal fluid(CSF), and obtained MRS from 12 patients. For mutational analysis, fibroblasts from skin biopy were obtained from 17 patients. We analyzed the T8993C or T9176C mutation at ATPase 6 gene. RESULTS: The male to female ratio is 12 to 5, and the age of onset is from 2 month to 8 year. Among the total 17 patients, 4 patients died, 4 patients alive yet, and 9 patients were unable to be followed up. The clinical manifestations were developmental delay or retardation(n=11, 64.7%), respiratory difficulty(n=10, 58.8%), altered consciousness (n=7, 41.2%), strabismus or ophthalmoplegia(n=5, 29.4%), feeding difficulty(n=5, 29.4%), etc. T2-weighted brain MRI showed bilateral high signal intensity in basal ganglia, brainstem, thalamus, periaqueductal gray matter, cerebral peduncle, substantia nigra, cerebellum, subcortical white matter. MRS was performed on 12 patients and showed lactate peak increase in ten patients(83.3%) and N-acetylaspartate peak decrease in two patients (16.7%). The concentrations of lactate and pyruvate in CSF and blood were obtained, and lactate/pyruvate ratio was calculated. We observed the elevation of ratio in 3(33.3%) of 9 cases in CSF, 7(63.6%) of 11 cases in blood, respectively. Our mutation analysis revealed that T8993C mutation in one patient and T9176C mutation in another patient were confirmed among the total 17 patients. CONCLUSION: Our study confirmed a case of the T8993C and a case of the T9176C mutation among 17 patients of Leigh syndrome. Therefore, Leigh syndrome is a genetically heterogenous disorder and further genetic study will be needed.
Adenosine Triphosphatases ; Age of Onset ; Basal Ganglia ; Brain ; Brain Stem ; Cerebellum ; Chungcheongnam-do ; Consciousness ; DNA, Mitochondrial ; Energy Metabolism ; Female ; Fibroblasts ; Humans ; Lactic Acid ; Leigh Disease* ; Magnetic Resonance Imaging ; Male ; Neurodegenerative Diseases ; Pediatrics ; Periaqueductal Gray ; Point Mutation ; Pyruvic Acid ; Skin ; Strabismus ; Substantia Nigra ; Tegmentum Mesencephali ; Thalamus