Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS)syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.

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Reversal of Stroke-Like Episodes With L-Arginine and Meticulous Perioperative Management of Renal Transplantation in a Patient With Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome. Case Report

The Neurohospitalist ◽

10.1177/19418744211000512 ◽

2021 ◽

pp. 194187442110005

Author(s):

Ghalia Al Yazidi ◽

Jaap Mulder ◽

Christoph Licht ◽

Elizabeth Harvey ◽

James Robertson ◽

...

Keyword(s):

Renal Transplantation ◽

Lactic Acidosis ◽

Mitochondrial Disorder ◽

Failure To Thrive ◽

Mitochondrial Encephalomyopathy ◽

Rapid Recovery ◽

Exercise Intolerance ◽

High Dose ◽

Melas Syndrome ◽

Facial Diplegia

Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder with recurrent non-arterial distribution stroke-like episodes (SLEs). A 17 yr old boy with MELAS (m.3243A>G tRNALeu(UUR)) presented with SLEs at ages 8 and 10 yrs. At 11 yrs, he suffered a third SLE involving left parietotemporal lobes with dense right hemiplegia and aphasia persistent for 1 week without improvement. On high dose IV L-Arginine (L-Arg) (0.5 g/kg/day divided TID) he had rapid recovery within 48 hours and was rapidly weaned. With emesis of oral L-Arg, his SLE recurred and he was again treated with high dose IV L-Arg with similar rapid recovery and discharged on a slow wean over 6 wks to 0.1 g/kg/day. On maintenance L-Arg he suffered only 2 SLEs at ages 13 and 16 yrs; both resolved rapidly with high dose IV L-Arg without recurrence during a slow wean to maintenance. His phenotype included seizures, ptosis, ophthalmoplegia, facial diplegia, sensorineural hearing loss, ataxia, myopathy, exercise intolerance, peripheral sensorimotor neuropathy, hypertrophic cardiomyopathy, hypertension, and failure to thrive. At 16 yrs he developed end-stage renal disease, due to MELAS, requiring hemodialysis and at 17 yrs he underwent cadaveric renal transplantation. His peri-operative protocol included strict maintenance of perfusion, oxygenation, normothermia, biochemical homeostasis and serum arginine concentrations during which time there were no neurologic decompensations. He was transitioned to oral L-citrulline maintenance therapy which maintained higher serum arginine concentrations with better tolerance. He had no SLEs or seizures in the ensuing 2 yrs.

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Status Epilepticus as the Initial Manifestation of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome

Journal of the Korean Neurological Association ◽

10.17340/jkna.2020.4.4 ◽

2020 ◽

Vol 38 (4) ◽

pp. 276-280

Author(s):

Joong-Goo Kim ◽

Chul-Hoo Kang ◽

Jay Chol Choi ◽

Jiyong Shin ◽

Min-Ju Kim ◽

...

Keyword(s):

Lactic Acid ◽

Status Epilepticus ◽

Genetic Testing ◽

Lactic Acidosis ◽

Mitochondrial Myopathy ◽

Mitochondrial Disorder ◽

Mitochondrial Encephalomyopathy ◽

Melas Syndrome ◽

Initial Manifestation ◽

Severe Lactic Acidosis

Mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS) is a multisystem mitochondrial disorder that is rarely observed in adulthood. We report a case of MELAS syndrome diagnosed in a 22-year-old man presented with status epilepticus (SE) without a preceding stroke-like episode. Genetic testing revealed a mutation of heteroplasmic m.3243A>G. MELAS should be suspected in patients with recurrent, uncontrolled SE with unexplained severe lactic acidosis.

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Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNALeu(UUR) A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes

Molecular and Cellular Biology ◽

10.1128/mcb.01614-09 ◽

2010 ◽

Vol 30 (9) ◽

pp. 2147-2154 ◽

Cited By ~ 78

Author(s):

Ronghua Li ◽

Min-Xin Guan

Keyword(s):

Lactic Acidosis ◽

Molecular Mechanism ◽

Wide Spectrum ◽

Trna Synthetase ◽

Mitochondrial Encephalomyopathy ◽

Therapeutic Interventions ◽

Trna Genes ◽

Mitochondrial Translation ◽

Mitochondrial Dysfunctions ◽

A3243g Mutation

ABSTRACT Mutations in mitochondrial tRNA genes are associated with a wide spectrum of human diseases. In particular, the tRNALeu(UUR) A3243G mutation causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms (MELAS) and 2% of cases of type 2 diabetes. The primary defect in this mutation was an inefficient aminoacylation of the tRNALeu(UUR). In the present study, we have investigated the molecular mechanism of the A3243G mutation and whether the overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) in the cytoplasmic hybrid (cybrid) cells carrying the A3243G mutation corrects the mitochondrial dysfunctions. Human LARS2 localizes exclusively to mitochondria, and LARS2 is expressed ubiquitously but most abundantly in tissues with high metabolic rates. We showed that the alteration of aminoacylation tRNALeu(UUR) caused by the A3243G mutation led to mitochondrial translational defects and thereby reduced the aminoacylated efficiencies of tRNALeu(UUR) as well as tRNAAla and tRNAMet. We demonstrated that the transfer of human mitochondrial leucyl-tRNA synthetase into the cybrid cells carrying the A3243G mutation improved the efficiency of aminoacylation and stability of mitochondrial tRNAs and then increased the rates of mitochondrial translation and respiration, consequently correcting the mitochondrial dysfunction. These findings provide new insights into the molecular mechanism of maternally inherited diseases and a step toward therapeutic interventions for these disorders.

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Migratory stroke-like lesions in a case of adult-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and a review of imaging findings

Radiology Case Reports ◽

10.1016/j.radcr.2016.09.003 ◽

2016 ◽

Vol 11 (4) ◽

pp. 425-429 ◽

Cited By ~ 6

Author(s):

Stephen S. Cai ◽

Rainer von Coelln ◽

Theresa J. Kouo

Keyword(s):

Lactic Acidosis ◽

Mitochondrial Encephalomyopathy ◽

Adult Onset ◽

Melas Syndrome ◽

Imaging Findings

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Detection of a new case harboring mitochondrial A3243G mutation of MELAS syndrome

VNU Journal of Science Natural Sciences and Technology ◽

10.25073/2588-1140/vnunst.4570 ◽

2017 ◽

Vol 33 (1S) ◽

Author(s):

Phung Bao Khanh ◽

Nguyen Minh Hoang ◽

Pham Van Anh ◽

Le Ngoc Anh ◽

Cao Vu Hung ◽

...

Keyword(s):

Mitochondrial Genome ◽

Lactic Acidosis ◽

Real Time ◽

Mutation Analysis ◽

Real Time Pcr ◽

Melas Syndrome ◽

Mitochondrial Encephalopathy ◽

Pcr Rflp ◽

A3243g Mutation ◽

Severity Of The Disease

Mitochondrial genome A3243G mutation in the tRNALeu(UUR) encodinggene (MTTL)is the main cause of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). This mutation exists in heteroplasmic form and severity of the disease is affected by many factors including heteroplasmy level. In this study, a pediatric proband (female, 8 years old) was found to carry A3243G mutation at 77.6% of heteroplasmy by using PCR-RFLP in combination with real-time PCR. The results of the A3243G mutation analysis of the proband’s family showed that her mother without any symptoms of encephalopathyalso carried the mutation at 7.9% of heteroplasmy whereas the mutation was not found in the proband’s healthy father and healthy sister, indicating that the proband received the A3243G mutation from her mother and the expression of MELAS syndromes depended on the level of heteroplasmy.

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Psychiatric Care For A Person With MELAS Syndrome: A Case Report

10.22541/au.161245869.94086141/v1 ◽

2021 ◽

Author(s):

Douglas Yeung Leong ◽

Rei Yen Chee ◽

Yit Shiang Lui

Keyword(s):

Case Report ◽

Lactic Acidosis ◽

Multidisciplinary Team ◽

Psychiatric Care ◽

Mitochondrial Encephalomyopathy ◽

Team Approach ◽

Melas Syndrome ◽

Team Members ◽

Multidisciplinary Team Approach

A patient with diagnosed MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome had developed psychological and behavioural disturbances at a later stage of his illness. Psychiatric care for this patient would not be possible without a multidisciplinary team approach involving multi-prong interventions from the different team members.

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