No abstract available.
Hypertension ; Leigh Disease*

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

Central Nervous System ; pathology ; Humans ; Infant ; Leigh Disease ; pathology ; physiopathology

Humans ; Leigh Disease/therapy* ; Consensus ; Brain ; DNA, Mitochondrial

PURPOSE: Leigh syndrome is a typical type of mitochondrial disease. This study was conducted to analyze the types of ophthalmologic symptoms and results of funduscopy conducted in the ophthalmologic examination of patients with Leigh syndrome. METHODS: Funduscopy was conducted on 24 subjects, who were chosen among those diagnosed as having mitochondrial respiratory chain complex defect and who were clinically suitable for the criteria of Leigh syndrome. Their clinical features, ophthalmologic symptoms, and ophthalmologic examination results were retrospectively analyzed. RESULTS: Of the 24 patients with Leigh syndrome, 11 developed ophthalmologic symptoms and no abnormal finding was observed in 13. The most frequent abnormal finding was visual disturbance in 5 patients. Funduscopy revealed abnormal findings in 17 patients; retinal pigmentation was the most frequent abnormality and was seen in 9 patients. CONCLUSION: Funduscopy can be an important screening test to find ophthalmologic abnormalities among patients with mitochondrial disease (MD), including those patients whose ophthalmologic symptoms are inconspicuous. It is predicted that an improved screening test can be made in the future that will identify risk factors related to ophthalmologic symptoms.
Electron Transport ; Humans ; Leigh Disease ; Mass Screening ; Mitochondrial Diseases ; Pigmentation ; Retinaldehyde ; Retrospective Studies ; Risk Factors

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* ; Diagnosis ; Humans ; Leigh Disease* ; Magnetic Resonance Imaging* ; Mamillary Bodies ; Neurodegenerative Diseases

PURPOSE: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. MATERIALS AND METHODS: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). RESULTS: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK ) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. CONCLUSION: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.
Classification ; Diagnosis ; DNA, Mitochondrial ; Humans ; Leigh Disease* ; MERRF Syndrome* ; Mitochondrial Diseases ; Phenotype

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.
Adolescent ; DNA, Mitochondrial ; genetics ; Electron Transport Complex I ; deficiency ; Humans ; Leigh Disease ; genetics ; Male ; Mutation

OBJECTIVETo investigate the value of functional magnetic resonance imaging (MRI) in sequential evaluation of patients with Leigh syndrome.

METHODSTwo patients with Leigh syndrome underwent diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and proton magnetic resonance spectroscopy ((1)H-MRS).

RESULTSThe brain lesions showed hyperintensity on DWI, lactate doublet peak on MRS and hyperperfusion in the patients at baseline, and maintained a hyperintensity on DWI and hyperperfusion in the absence of lactate doublet peak on MRS at follow-up 1 year later. DWI still revealed persistent hyperintensity in the brain lesions in one patient 2 years later.

CONCLUSIONFunctional MRI can sensitively highlight the characteristics of brain lesions in patients with Leigh syndrome, and can therefore be used to evaluate the sequential changes of the brain lesions.

Brain ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Leigh Disease ; pathology ; Magnetic Resonance Imaging ; methods

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs' cycle. Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome. In this study, one Chinese case of PDHA1 deficiency was reported. The patient was a boy with normal mental development, retarded motor development, general weakness, hypotonia and areflexia. Muscle histopathological findings suggested axonal peripheral neuropathy. Brain magnetic resonance imaging at 5 years of age revealed bilateral putamina lesions and periventricular white matter demyelination, supporting the diagnosis of Leigh syndrome. A C214T mutation in exon 3 of the PDHA1 gene was detected. After the treatment of thiamin, coenzyme Q10, Lcarnitine and carbohydrates-restricted diet, his movement ability improved significantly. At present, the patient is 8 years old and has normal school life. PDHA1 deficiency is an X-linked inherited metabolic disease, which shares various clinical manifestations and leads to difficult diagnosis. This patient predominately presented with progressive weakness and was diagnosed by gene analysis.
Child, Preschool ; Diagnosis, Differential ; Humans ; Leigh Disease ; diagnosis ; genetics ; therapy ; Male ; Mutation ; Pyruvate Dehydrogenase (Lipoamide) ; genetics