Burden of Proof in the Postmortem Diagnosis of Mitochondrial Disease: Leigh Disease

Excerpt

This male infant weighed 6 lb 12 oz after a full-term pregnancy. At age 2 to 3 months, he had been diagnosed with hypertrophic cardiomyopathy, hypotonia, lactic acidosis, and poor control of oral feeds. He had gastroesophageal reflux and subsequently required nasogastric tube feeds. Gastrostomy button, fundoplication, and a left thigh muscle biopsy were performed. The biopsy showed features “suggestive of” a mitochondrial myopathy, and subsequent mitochondrial enzyme analyses showed decreased activities in complexes I through IV that approached statistical significance but were not quite at 2 standard deviations below the normal reference mean. Ophthalmologic examination was normal, and magnetic resonance imaging of the head was normal except for extra axial fluid collections. …