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Melas: an original case and clinical criteria for diagnosis
M Hirano1, E Ricci, M R Koenigsberger
1Department of Neurology, H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia-Presbyterian Medical Center, New York, New York.
Abstract:
We describe the full history and postmortem findings in one of the first identified cases of mitochondrial encephalomyopathy with stroke-like episodes (MELAS). To clarify diagnostic criteria, we analyzed 69 reported cases. The syndrome should be suspected by the following three invariant criteria: (1) stroke-like episode before age 40 yr; (2) encephalopathy characterized by seizures, dementia, or both; and (3) lactic acidosis, ragged-red fibers (RRF), or both. The diagnosis may be considered secure if there are also at least two of the following: normal early development, recurrent headache, or recurrent vomiting. There are incomplete syndromes in relatives of patients with the full syndrome and incomplete syndromes might also be encountered in sporadic cases. Some MELAS patients have features of the Kearns-Sayre syndrome (KSS) or myoclonic epilepsy with ragged-red fibers (MERRF), but none had the full KSS syndrome. In partial or confusing cases, analysis of mitochondrial DNA (mtDNA) may point to the correct diagnosis; however, not all patients with clinical MELAS have had the typical mtDNA point mutation and some patients with the mutation have clinical syndromes other than MELAS.
Insights
Mitochondrial encephalomyopathy with stroke-like episodes (MELAS) requires specific diagnostic criteria including stroke-like episodes, encephalopathy, and lactic acidosis or ragged-red fibers. Genetic analysis of mitochondrial DNA (mtDNA) aids in diagnosing MELAS, especially in complex cases.
Area of Science:
- Neurology
- Genetics
- Mitochondrial Diseases
Background:
- Mitochondrial encephalomyopathy with stroke-like episodes (MELAS) is a rare genetic disorder.
- Accurate diagnosis is crucial for patient management and understanding disease progression.
Observation:
- Analysis of 69 reported cases and a detailed case history.
- Identified invariant criteria for MELAS suspicion: stroke-like episodes before 40, encephalopathy (seizures/dementia), and lactic acidosis/ragged-red fibers (RRF).
- Additional criteria for secure diagnosis include normal early development, recurrent headache, or vomiting.
Findings:
- Established clear diagnostic criteria for MELAS, including invariant and supportive features.
- Observed incomplete syndromes in relatives and sporadic cases.
- Noted overlap with Kearns-Sayre syndrome (KSS) and myoclonic epilepsy with ragged-red fibers (MERRF), but no full KSS.
- Mitochondrial DNA (mtDNA) analysis is valuable but not universally definitive; some MELAS cases lack the typical mutation, and some with the mutation present differently.
Implications:
- The defined criteria will aid in earlier and more accurate MELAS diagnosis.
- Highlights the genetic heterogeneity and phenotypic variability of MELAS.
- Emphasizes the role of mtDNA analysis in complex or atypical presentations.