Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
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Overview of Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes (MELAS) syndrome

멜라스 증후군의 개요

  • Ji-Hoon Na (Departments of Pediatrics, Gangnam Severence Hospital, Yonsei University College of Medicine) ;
  • Young-Mock Lee (Departments of Pediatrics, Gangnam Severence Hospital, Yonsei University College of Medicine)
  • 나지훈 (연세대학교 의과대학 강남세브란스병원 소아청소년과학교실) ;
  • 이영목 (연세대학교 의과대학 강남세브란스병원 소아청소년과학교실)
  • Published : 2024.06.30
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Abstract

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.

MELAS 증후군은 다양한 임상 증상을 나타내는 복잡하고 다면적인 미토콘드리아 질환으로, 반복적인 뇌졸중 유사 에피소드, 발작, 당뇨병, 심근병증 등을 포함한다. 이러한 증상들은 뇌, 심장, 근육과 같은 대사적으로 활발한 조직에 미토콘드리아 기능 장애가 미치는 심각한 영향을 반영한다. 현재의 치료는 이러한 증상을 완화하고 미토콘드리아 기능을 개선하는 데 중점을 두고 있으며, 증상 치료, 고용량 비타민 요법 및 고용량 타우린 보충과 같은 혁신적인 접근 방식을 포함한다. 유전자 치료 및 미토콘드리아 표적 약물 분야의 새로운 치료법은 근본적인 유전자 돌연변이를 해결하고 미토콘드리아 건강을 향상시킬 수 있는 유망한 새로운 길을 제공한다. MELAS에 대한 이해가 계속 깊어짐에 따라, 유전자 검사 및 치료적 개입의 발전은 환자의 결과를 크게 개선할 가능성을 갖고 있다. MELAS 치료의 미래는 낙관적이며, 진행 중인 연구는 더 효과적이고 표적화된 치료법을 위한 길을 열어 이 질환의 부담을 줄이고 영향을 받는 개인들의 삶의 질을 향상시키는 것을 목표로 하고 있다.

Keywords

Acknowledgement

We would like to express our sincere appreciation to the patients with MELAS, their families, and the medical staff members. Additionally, we are profoundly thankful to the generous donors whose financial support and interest in the treatment of rare neurodegenerative diseases have made this research possible.

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