Foundations · Year 1 · from Foundations
Case 2: Leigh Syndrome (Mitochondrial Disease)
Clinical Image
Source: Radiopaedia - Leigh syndrome - CC BY-NC-SA 3.0
Case Presentation
A 14-month-old boy presents with progressive developmental regression over 3 months. He had been meeting milestones normally until 11 months of age but has since lost the ability to sit independently and has become increasingly hypotonic. His parents also note episodes of vomiting and irritability. Physical examination reveals generalized hypotonia, absent deep tendon reflexes, and dystonic posturing. He has difficulty swallowing and episodes of apnea. Laboratory studies show elevated serum lactate at 6.5 mmol/L and an elevated lactate-to-pyruvate ratio. MRI brain reveals symmetric T2 hyperintense lesions in the basal ganglia (particularly putamen) and brainstem, characteristic of Leigh syndrome. Genetic testing identifies a mutation in the SURF1 gene, which affects cytochrome c oxidase (complex IV) assembly. He is started on supportive care including coenzyme Q10 and thiamine supplementation. The family is counseled about the poor prognosis of this progressive neurodegenerative condition.
Key Learning Points
- Leigh syndrome results from defects in mitochondrial energy production, including mutations affecting pyruvate dehydrogenase complex, TCA cycle enzymes, or respiratory chain components
- Elevated lactate and elevated lactate-to-pyruvate ratio indicate impaired mitochondrial function; pyruvate accumulates and is converted to lactate when it cannot enter or proceed through the TCA cycle normally
- The characteristic bilateral symmetric lesions in basal ganglia and brainstem reflect the high metabolic demands of these structures and their vulnerability to energy failure