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The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study
Benjamin C Cox1, Jennifer Y Pearson1, Jay Mandrekar2
1Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN, United States.
Objective:
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity.
Methods:
We reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as "standard-onset" if the first stroke-like episode (SLE) occurred before age 40 or "late-onset."
Results:
Eighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p < 0.05). There was a trend toward higher serum heteroplasmy in MELAS compared to symptomatic non-MELAS and asymptomatic (means 39.3, 29.3, and 21.8% p = 0.09). Symptomatic non-MELAS had more sensorineural hearing loss as first presenting symptom (51.6% vs. 24.4%, p < 0.05). MELAS had higher prevalence of seizures (88.1% vs. 16.7%, p < 0.05) and shorter survival from onset to death (50% mortality at 25 years vs. 10%, p < 0.05). Late-onset MELAS had longer disease duration from first symptom to first SLE (mean 16.6 vs. 9.3 yrs) and also lived longer (mean age at death 62 vs. 30). Standard-onset MELAS had more neurologic involvement at onset than late-onset (51.7% vs. 15.4%). Late-onset patients had more prevalent diabetes (69.2% vs. 13.8%) and nephropathy (53.8% vs. 10.3%). Patients with late-onset MELAS also had more organ systems involved (mean 4.1 vs. 2.7, p < 0.05). There was a trend toward higher heteroplasmy levels in standard-onset (mean 44.8% vs. 25.3%, p = 0.18).
Discussion:
Our study highlights the spectrum of MELAS. The lower BMI in MELAS at presentation as well as higher rates of sensorineural hearing loss as initial symptom in symptomatic non-MELAS may be useful clinical markers. While many patients present before age 40 with SLE, some can present with SLE later in life. Standard onset MELAS is more likely to present with neurologic symptoms. Late-onset is more likely to suffer diabetes or nephropathy and have more organ systems involved.
Insights
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) presents a spectrum from severe to mild, with lower BMI and higher seizure rates indicating MELAS. Late-onset MELAS patients experience more diabetes and nephropathy, highlighting distinct clinical patterns.
Area of Science:
- Genetics and Genomics
- Neurology
- Mitochondrial Diseases
Background:
- Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disorder with variable clinical presentations.
- Understanding the full clinical spectrum, from affected individuals to asymptomatic carriers, is crucial for accurate diagnosis and management.
- Identifying predictors of disease severity can aid in prognostication and therapeutic strategies.
Purpose of the Study:
- To evaluate the clinical spectrum of MELAS, encompassing patients with MELAS, symptomatic non-MELAS individuals, and asymptomatic carriers.
- To identify clinical and genetic factors that predict disease severity in MELAS.
- To differentiate characteristics between standard-onset and late-onset MELAS.
Main Methods:
- Retrospective review of 81 patients with MELAS or positive genetic findings without meeting full clinical criteria.
- Classification into MELAS, symptomatic non-MELAS, and asymptomatic groups based on clinical criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE).
- Subcategorization of MELAS into standard-onset (SLE before age 40) and late-onset.
Main Results:
- MELAS patients exhibited lower BMI at onset and a higher prevalence of seizures compared to other groups.
- Symptomatic non-MELAS patients were more likely to present with sensorineural hearing loss.
- Late-onset MELAS patients had a longer disease duration, increased survival, and higher rates of diabetes and nephropathy, with more organ systems involved.
Conclusions:
- The clinical spectrum of MELAS is broad, with distinct features differentiating patient groups.
- Lower BMI at presentation and higher seizure rates are associated with MELAS.
- Late-onset MELAS presents unique challenges, including higher rates of diabetes and nephropathy, and broader organ system involvement.
