1.Leigh Syndrome in a Filipino Child: A case report.
Michelle G. SY ; Ma. Antonia Aurora MORAL-VALENCIA
Journal of Medicine University of Santo Tomas 2022;6(2):1027-1038
Introduction:
Leigh disease and Leigh-like syndrome are a heterogenous group of neurodegenerative disorders involving any level of the neuraxis and may present with a variety of clinical presentations, prominent among them is psychomotor regression. Despite the remarkable number of established disease genes and novel mutations being discovered, many cases of Leigh syndrome remain without a genetic diagnosis, indicating that there are still more disease genes to be identified.
Case:
Here we present a case of a two and a half-year-old girl who presented with delayed acquisition of developmental milestones with subsequent regression, ataxia, and dyskinesia. Her work-up showed raised blood lactate levels and lactate peak in MR spectroscopy. Mitochondria genome showed absence of mitochondrial DNA mutation, while whole exome sequence analysis revealed a novel dynein gene variant, p.A1577S. Her parents underwent genetic testing as well, and her father also had the same dynein mutation, however, is non-symptomatic. She had an older brother who initially presented with ophthalmoplegia and eventually developed psychomotor regression. He subsequently expired from respiratory failure after almost 2 years from initial presentation. Both siblings were diagnosed with Leigh syndrome.
Conclusion
The diagnosis of Leigh syndrome remains based on characteristic clinical and radiologic findings. However, a specific defect must be identified if reliable genetic counseling is to be provided.
Neurodegenerative Diseases|leigh Disease
2.Serial MRI Findings in a Clinically Diagnosed Adult Onset Leigh Syndrome.
Sung Eun KIM ; Jae Young KIM ; Jung Wook JUNG ; Dong Sun KIM ; Eun Ju JUNG ; Eung Kyu KIM ; Seok Hyun SON ; Choong Ki EUN ; Tae Yoon LEE
Journal of the Korean Neurological Association 2000;18(3):341-344
Adult onset Leigh syndrome is a very rare neurodegenerative disorder of unknown cause. We report the evolution of the lesions on serial MRIs in a 38-year-old man with clinically diagnosed Leigh syndrome. We emphasize that the mammillary bodies can be involved during the disease course and that premortem diagnosis of Leigh syndrome is pos-sible, if a characteristic distribution of lesions can be demonstrated on MRI.
Adult*
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Diagnosis
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Humans
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Leigh Disease*
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Magnetic Resonance Imaging*
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Mamillary Bodies
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Neurodegenerative Diseases
3.Leigh Syndrome: Subgroup Aanalysis according to Mitochondrial DNA Mutation.
Na Lee JEE ; Sun Mi HER ; Se Hoon KIM ; Min Jung LEE ; Chul Ho LEE ; Young Mock LEE
Journal of the Korean Child Neurology Society 2018;26(1):7-12
PURPOSE: Leigh syndrome (LS) is a rare, progressive neurodegenerative disorder with characteristic abnormalities in the central nervous system. Such patients present with heterogeneous clinical symptoms and genetic abnormalities; thus, prognosis is difficult to anticipate. The present study investigates whether distinct patient characteristics are associated with mitochondrial DNA (mtDNA) mutation in LS patients. METHODS: We retrospectively analyzed data from patients diagnosed with LS at our hospital who were assessed using genomic sequencing of mtDNA. A subgroup analysis was performed to divide patients according to the mtDNA sequencing results. RESULTS: Among the 85 patients enrolled, 18 had mtDNA mutations. Most patients had lactic acidosis and a lactate/pyruvate ratio above 20, indicating respiratory chain abnormalities. In the subgroup analysis, the mutation group had a significantly higher female-to-male ratio, alanine level, ocular involvement, and midbrain and medulla abnormalities on magnetic resonance imaging (MRI). CONCLUSION: The subgroup analysis indicates that mtDNA sequencing is recommended for female patients, or those who exhibit ocular involvement, high alanine levels, or MRI findings with lesions in the midbrain and medulla.
Acidosis, Lactic
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Alanine
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Brain Stem
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Central Nervous System
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DNA, Mitochondrial*
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Electron Transport
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Female
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Humans
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Leigh Disease*
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Magnetic Resonance Imaging
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Mesencephalon
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Mitochondria
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Neurodegenerative Diseases
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Prognosis
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Retrospective Studies
4.Leigh Syndrome: Clinical, Radiological, and Mitochondrial Mutational Study.
Deok Soo KIM ; Tae Sung KO ; Han Wook YOOZ
Journal of the Korean Child Neurology Society 2002;10(1):111-121
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
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Age of Onset
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Basal Ganglia
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Brain
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Brain Stem
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Cerebellum
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Chungcheongnam-do
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Consciousness
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DNA, Mitochondrial
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Energy Metabolism
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Female
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Fibroblasts
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Humans
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Lactic Acid
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Leigh Disease*
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Magnetic Resonance Imaging
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Male
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Neurodegenerative Diseases
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Pediatrics
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Periaqueductal Gray
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Point Mutation
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Pyruvic Acid
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Skin
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Strabismus
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Substantia Nigra
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Tegmentum Mesencephali
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Thalamus