MELAS syndrome: correlation between clinical features and molecular genetic analysis

Area of Science:

• Genetics
• Neurology
• Mitochondrial Diseases

Background:

• Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited disorder.
• Clinical presentation and genetic basis of MELAS can vary significantly among affected individuals and families.

Observation:

• A Taiwanese family with a female proband presenting with stroke-like episodes, neurological deficits, short stature, hearing impairment, and elevated lactate levels was investigated.
• Muscle biopsies revealed paracrystalline inclusion bodies and NADH-CoQ reductase deficiency, despite the absence of ragged-red fibers.
• Mitochondrial DNA (mtDNA) analysis identified an A-to-G mutation at nucleotide pair 3243 in the mitochondrial transfer RNA(Leu) gene in maternal relatives.

Findings:

• The identified mtDNA mutation (m.3243A>G) was present in blood, hair follicles, and muscle tissues of affected maternal relatives.
• Heterogeneous distribution of mutated mtDNA was observed across different tissues and individuals within the family.
• The proband exhibited a higher proportion of mutated mtDNA compared to asymptomatic or mildly symptomatic relatives.

Implications:

• The variable clinical phenotypes in this MELAS family are partly explained by the differing proportions of mutant mtDNA in target tissues.
• Understanding mtDNA heteroplasmy is crucial for diagnosing and managing MELAS syndrome.
• This case highlights the importance of comprehensive genetic analysis and family studies in mitochondrial disorders.