• Journal of Genetic Medicine
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• v.21 no.1
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• pp.36-40
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• 2024

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome is a maternally inherited mitochondrial disorder that usually affects the cerebral cortex and prevents high-energy demands from being met. Herein, we present the case of a male patient who rapidly developed multiple seizures, headaches, and altered mentality accompanied by severe metabolic acidosis and lactic acidosis. Initially, a brain imaging study confirmed stroke-like lesions (SLLs) only in the cerebellum. During follow-up, newly developed SLLs with lactic acidosis were observed in the basal ganglia (BG), cerebellum, and occipital lobe. The m.3243A>G variant had been found in the patient and MELAS was diagnosed, despite the BG and cerebellum being atypical locations for SLLs in MELAS. Since most cases of m.3243A>G variant MELAS show SLLs in the cerebral cortex, this case is unusual considering the location of the lesion. We emphasize that in the case of lactic acidosis accompanied by neurological symptoms, such as seizures, as in this case, MELAS should be included in the differential diagnosis, even if SLLs are observed in areas other than the cerebral cortex.

• Proceedings of the KSMRM Conference
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• 2000.11a
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• pp.59-59
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• 2000

• Journal of The Korean Society of Inherited Metabolic disease
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• v.24 no.1
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• pp.1-9
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• 2024

Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episode (MELAS) is a rare maternally inherited disorder primarily caused by mutations in mitochondrial DNA, notably the m.3243A>G mutation in the MT-TL1 gene. This mutation impairs mitochondrial function crucial for cellular energy production, particularly in high-energy-demanding organs such as the brain and muscles. MELAS manifests as recurrent stroke-like episodes, seizures, diabetes mellitus, cardiomyopathy, and other multisystemic symptoms that are often present in childhood. The diagnosis combines genetic testing, clinical evaluation, and neuroimaging, with elevated lactate levels and characteristic magnetic resonance imaging (MRI) findings as key indicators. Treatment focuses on symptomatic management and enhancement of mitochondrial function through L-arginine, coenzyme Q10, high-dose vitamins, and taurine supplementation. Studies have identified additional genetic variants linked to MELAS, including mutations in POLG and other mitochondrial genes, further complicating the genetic landscape. Emerging therapies, particularly gene therapy and mitochondria-targeting drugs, offer promising avenues for addressing the underlying genetic defects and improving mitochondrial functioning. Furthermore, ongoing studies continue to enhance our understanding and management of MELAS, with the aim of reducing its burden and improving patient outcomes and quality of life. This review summarizes the current knowledge on the genetics, clinical features, diagnosis, and treatment of MELAS, highlighting the latest advancements and future directions for therapeutic interventions.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.102-108
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• 2016

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome is one of mitochondrial encephalopathy. As the early clinical manifestations can be variable, it is important to suspect the disease, especially in patients with multiple organ dysfunctions. A boy was diagnosed with epilepsy when he was 9 years old. Two years later, severe headache and blurred vision developed suddenly. On examination, left homonymous hemianopsia was detected with corresponding cerebral parenchymal lesions in right temporo-occipito-parietal areas. MELAS syndrome was confirmed by genetic test, which showed m.3243 A>G mitochondrial DNA mutation. Multivitamins including coenzyme Q10 were added to anticonvulsant. He experienced 4 more events of stroke-like episodes over 5 years, but he is able to perform normal daily activities. A 13-year-old boy was brought to the hospital due to suddenly developed respiratory arrest and asystole associated with pneumonia. Past medical history revealed that he had multiple medical problems such as epilepsy, failure-to-thrive, optic atrophy, and deafness. He has been on valproic acid as an anticonvulsant which was prescribed from local clinic. He recovered after the resuscitation, but his cognition and motor function were severely damaged. He became bed-ridden. He was diagnosed with MELAS syndrome by brain MRI, muscle biopsy, and clinical features. Genetic test did not reveal any mitochondrial gene mutation. Four years later, he expired due to suddenly developed severe metabolic acidosis combined with hyperglycemic hyperosmolar nonketotic coma. The clinical features of MELAS syndrome are variable. Early diagnosis before the presentation to the grave clinical course may be important for the better clinical outcome.

• Annals of Clinical Neurophysiology
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• v.24 no.2
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• pp.84-89
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• 2022

Vestibular dysfunction has rarely been reported in MELAS syndrome. A 40-year-old male with long-term diabetes and hearing loss experienced a stroke-like episode with hemisensory disturbance and lactic acidosis. Brain MRI showed temporo-parieto-occipital cortical lesions, and a final diagnosis was made of MELAS syndrome with the mitochondrial 3243A>G mutation. Neuro-otologic evaluations revealed anterior-canal-sparing bilateral impairments of the vestibulo-ocular reflex in the video head impulse test and no caloric paresis. This unique pattern of vestibular dysfunction may aid in diagnosing MELAS syndrome.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.77-79
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• 2002

The urea cycle, consisting of a series of six enzymatic reactions, plays key roles to prevent the accumulation of toxic nitrogenous compound and synthesize arginine de novo. Five well characterized diseases have been described, resulting from an enzymatic defect in the biosynthesis of one of the normally expressed enzyme. This presentation will focus on two representative diseases; ornithine transcarbamylase(OTC) deficiency and citrullinemia(argininosuccinate synthetase deficiency). OTC deficiency is one of the most common inborn error of urea cycle, which is inherited in X-linked manner. We identified 17 different mutations in 20 unrelated Korean patients with OTC deficiency; L9X, R26P, R26X, T44I, R92X, G100R, R141Q, G195R, M205T, H214Y, D249G, R277W, F281S, 853 del C, R320X, V323M and 10 bp del at nt. 796-805. These mutations occur at well conserved nucleotide sequences across species or CpG hot spot. The L9X and R26X lead to the disruption of leader sequences, required for directing mitochondrial localization of the OTC precursor. Their phenotypes are severe, and neonatal onset. The G100R, R277W and V323M mutations were uniquely identified in patients with late onset OTC deficiency. The other genotypes are associated with neonatal onset. Out of 20 patients with OTC deficiency, only 6 patients are alive; two were liver transplanted, and normal in growth and development at 2, 4 years after transplantation respectively. Citrullinemia is an autosomal recessive disease, caused by the mutations in the argininosuccinate synthetase(ASS) gene. We identified in 3 major mutations in 11 unrelated Korean patients with citrullinemia; G324S, $IVS6^{-2}$ A to G, and 67 bp ins at nt 1125-1126. Among these, the 67 base pair insertion mutation is novel. The allele frequency of each mutation is; G324S(45%), IVS6-2 A to G(32%), and 67 base pair insertion(14%). All patients are diagnosed at neonatal or infantile age. Interestingly, two patients presented with stroke like episode. Out of 11 patients, 5 patients died. Among 6 patients alive, one patient was successfully liver transplanted.

• Journal of Electrodiagnosis and Neuromuscular Diseases
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• v.20 no.2
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• pp.106-111
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• 2018

Transcranial magnetic stimulation (TMS) has been a gold standard for investigating central motor pathways in humans. Diffusion tensor imaging with fiber tractography (DTI FT) is known for its usefulness in detecting white matter lesion in vivo. We investigated the clinical usefulness of elucidating the integrity and continuity of corticospinal tract (CST) by combined use of TMS and DTI FT in this study. We report two cases who have presented with left hemiparesis and evaluated by both TMS and DTI FT; 10-year-old boy with Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episode syndrome and 20-year-old woman with traumatic brain injury. Combined use of TMS and DTI FT successfully led to localize the brain lesion that might cause motor impairment in patients with abnormal signal intensities in MRI. The results of this study suggest that TMS and DTI FT might provide the detailed information between function and anatomy of the CST, complementarily.