II. Definitions
III. Epidemiology
IV. Pathophysiology
- Maternally inherited (as with all mitochondrial disorders)
- Multiple genetic defects cause MELAS, but a single base pair mutation m.3234>G is found in 80% of cases
- Progressive mitochondrial disorder primarily affects nerve and Muscle Tissue (highly metabolically active cells)
- tRNA mutations alter respiratory chain complex synthesis
- Impaired mitochondrial energy production, resulting in anaerobic activity and Lactic Acidosis
- Microvascular angiopathy
- Impaired cerebral vasodilation
V. Findings
- Recurrent Neurologic Episodes
- Encephalopathy
- Altered Level of Consciousness with episodes
- Longterm gradual deterioration of overall cognitive function
- Myopathy
- Proximal Muscle Weakness
- Exercise intolerance
- Migraine Headache
- Focal neurologic deficits (stroke-like episodes)
- Most commonly presents with Hemiparesis, Hemianopia
- Do not follow a typical vascular pattern
- Cummulative stroke-like events result in progressive neurologic deficits
- MRI demonstrates correlating lesions
- Seizures
- Focal or Generalized Seizures
- Younger age of onset may predispose to treatment refractory Seizures
- Encephalopathy
- Other Findings in Children
- Growth and development is typically normal until symptom onset and diagnosis
- Short Stature is common
- Less common onset in infants, may be associated with Failure to Thrive, congenital Deafness
VI. Labs
- Lactic Acidosis
-
Muscle Biopsy: Compensatory mitochondrial proliferation
- Ragged Red fibers on Gomori Trichome stain
- Perivascular Smooth Muscle reacts to succinate dehydrogenase
VII. Diagnosis
- Stroke-Like Events before age 40 years old
- Encephalopathy with Seizures and Dementia
- Serum Lactic Acidosis
- Muscle biopsy with ragged red fibers
VIII. Differential Diagnosis
- Kearns-Sayre
- Associated with Short Stature, Hearing Loss and Ataxia
- Distinguished by its Vision related findings (Ophthalmoplegia, Retinal changes) and cardiac defects
- Myoclonus Epilepsy with ragged red fibers (MERRF)
- Leigh Syndrome
IX. Associated Conditions
- Cardiac Conduction Deficits
- Diabetes Mellitus
X. Imaging
-
MRI Brain
- Multifocal infarcts that do not follow typical vascular patterns
XI. Management
- No specific MELAS treatments are available
- Keep Immunizations updated
-
Seizure Prophylaxis
- Avoid Valproate
-
Vitamin Supplementation
- Coenzyme Q10, Creatine and L-Carnitine
- May increase mitochondrial energy production and slow disease
- L-Arginine
- Coenzyme Q10, Creatine and L-Carnitine
- Avoid medications that may provoke disease
- Valproate (see Seizures above)
- Metformin (risk of Lactic Acidosis)
- Dichloroacetate (Peripheral Neuropathy risk)
- Mitochondrial toxins
XII. Resources
- Pia (2022) MELAS Syndrome, StatPearls, Treasure Island, FL