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An 18-year-old male patient presented with clinical and radiological evidence of Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia 11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional degenerative change in the cerebellum and dentate and olivary nuclei, and an axonal peripheral neuropathy. Biochemical studies showed reduced activity of complexes I and IV of the respiratory chain in mitochondria from heart, liver and kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly associated with the syndrome of myoclonic epilepsy and ragged red fibres, was detected in the patient's blood and was present in muscle, brain, liver, heart, and kidney in uniformly high amounts. It is clear that LS is genetically heterogeneous and represents one of the most severe phenotypes of a number of different mtDNA defects.

Nine cases of infantile spinal muscular atrophy were studied post-mortem. Their ages at death ranged from 5 months to 10 years. In all cases severe loss of anterior horn cells in the spinal cord and neurogenic muscular atrophy were characteristic of this disease. In 6 cases there was also loss of myelin in the posterior columns particularly affecting the lumbar contribution. Sensory ganglia, especially from the lumbar region, contained nodules of Nageotte, indicating sensory neuron degeneration. These sensory abnormalities were more severe in the longer surviving cases. It seems possible that sensory neuron degeneration occurs more commonly in Werdnig-Hoffmann disease than has previously been supposed but that it is less severe and develops more slowly than motor neuron degeneration.