MELAS Syndrome: Can It Occur in Men?
Yes, MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) can definitely occur in men, and some evidence suggests that male gender may actually be a risk factor for developing stroke-like episodes in patients with the m.3243A>G mutation.
What is MELAS?
MELAS is a multi-organ mitochondrial disorder characterized by:
- Mitochondrial myopathy (muscle disease)
- Encephalopathy (brain dysfunction)
- Lactic acidosis (buildup of lactic acid in the bloodstream)
- Stroke-like episodes that don't conform to specific arterial territories
Epidemiology and Gender Distribution
MELAS can affect both males and females, with some interesting gender-related observations:
- In a study of Italian m.3243A>G mutation carriers, researchers observed that male gender could represent a risk factor for developing stroke-like episodes 1
- In another study examining MELAS/Leigh Syndrome overlap, 9 out of 14 patients (64%) were male 2
Genetic Basis
MELAS is primarily caused by mutations in mitochondrial DNA:
- The most common mutation is m.3243A>G in the MT-TL1 gene (found in approximately 80% of MELAS patients) 3, 4
- Other mutations in mitochondrial genes can also cause MELAS, particularly in the MTND genes 2
- Since mitochondrial DNA is maternally inherited, the disease can be transmitted by mothers to children of both sexes
Clinical Manifestations
The cardinal features of MELAS include:
- Stroke-like episodes (not conforming to vascular territories)
- Exercise intolerance
- Seizures
- Lactic acidosis
- Ragged-red fibers on muscle biopsy
- Onset typically before 40 years of age 5
Additional common symptoms include:
- Migraine-like headaches
- Cognitive impairment
- Hearing impairment
- Diabetes
- Short stature 3
Diagnosis
Diagnosis of MELAS should be considered in patients with:
- Recurrent stroke-like episodes, especially with atypical features
- Elevated serum lactic acid levels, particularly during attacks
- Family history suggesting maternal inheritance
- MRI showing lesions that don't conform to vascular territories, especially in posterior cerebral hemispheres 5
Definitive diagnosis requires:
- Genetic testing showing the m.3243A>G mutation or other mitochondrial DNA mutations
- Blood leukocyte DNA reveals the A3243G mutation in 80% of MELAS patients 5
Treatment Options
There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team:
- L-arginine therapy has shown promise in unblinded studies for improving stroke-like episode symptoms and decreasing their frequency and severity 3
- Other commonly used supplements (though without proven efficacy) include:
Important Clinical Considerations
- MELAS can present at any age, including late adulthood (a case has been reported in a 63-year-old female) 6
- The disease has significant phenotypic variability, even among patients with the same mutation
- MELAS can overlap with other mitochondrial syndromes such as Leigh syndrome 2
- The stroke-like syndrome in MELAS is likely due to altered cellular metabolism affecting small cerebral vessels or dysfunction of autoregulatory mechanisms 5
Conclusion
MELAS is a mitochondrial disorder that affects both men and women. The disease shows considerable clinical heterogeneity, and interestingly, some evidence suggests males may have a higher risk of developing stroke-like episodes. Diagnosis requires a high index of suspicion, especially in patients with recurrent stroke-like episodes that don't follow typical vascular patterns, combined with other systemic manifestations.