Clinical Scenario:
A 9-year-old girl presents with recurrent episodes of headache, vomiting, and seizures. Her parents report that she has gradually developed difficulty with exercise tolerance and muscle weakness. During an acute episode, she develops transient right-sided weakness and visual disturbance. Laboratory investigations show elevated serum lactate levels. MRI brain demonstrates stroke-like lesions that do not correspond to vascular territories. Which of the following is the most likely diagnosis?
A) Acute disseminated encephalomyelitis
B) Glutaric acidemia type I
C) MELAS syndrome
D) Urea cycle disorder
E) Wilson disease
Correct answer & Explanation:
Correct Answer:
C) MELAS syndrome
Explanation:
This child has MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes), a mitochondrial disorder caused most commonly by mutations in mitochondrial DNA (especially MT-TL1 gene mutation).
Key Clinical features:
- Childhood onset
- Seizures
- Headache and vomiting
- Exercise intolerance and muscle weakness
- Elevated lactate due to impaired oxidative phosphorylation
- Stroke-like episodes
- MRI lesions crossing vascular territories
Why Option C is correct:
Mitochondrial dysfunction causes impaired ATP production, leading to energy failure in tissues with high metabolic demands, especially the brain and skeletal muscle.
Management includes:
- Supportive care
- Avoidance of mitochondrial toxins (e.g., valproate in certain mitochondrial disorders)
- Mitochondrial supplements such as coenzyme Q10 and L-arginine/citrulline in selected patients
- Management is primarily supportive and multidisciplinary. L-arginine has been used for stroke-like episodes, but evidence for arginine, citrulline, coenzyme Q10 and other supplements remains limited and unproven
Why other options are incorrect:
A) Acute disseminated encephalomyelitis
- Usually follows infection/vaccination and shows multifocal inflammatory demyelinating lesions, not lactic acidosis or recurrent stroke-like episodes.
B) Glutaric acidemia type I
- Causes dystonia and basal ganglia injury, usually with macrocephaly and characteristic organic acid abnormalities.
D) Urea cycle disorder
- Causes hyperammonemia and encephalopathy but not stroke-like lesions with elevated lactate.
E) Wilson disease
- Causes liver disease and movement disorders with copper accumulation, not lactic acidosis.
References
Mancuso M, Bellusci M, Carelli V, et al. Diagnostic criteria and management of MELAS and stroke-like episodes: consensus-based statements. Eur J Neurol. 2026;33(4):e70588. doi:10.1111/ene.70588.
You can also practice another MCQ on Metabolic disorder presented with hypotonia and cardiomegaly.
