Neuronal RNA metabolism in infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) studied by radioautography: a new technic in the investigation of neurological disease.

Abstract

Infantile spinal muscular atrophy, or Werdnig-Hoffmann's disease (1, 2) is a hereditary disorder causing progressive degeneration of the lower motor neurons. Transmitted as an autosomal recessive trait, it begins before birth or within the first 2 years of life and ends fatally, usually by the age of 2 to 5 years. Clinically, the disease is manifested by hypokinesia, hypotonia, loss of tendon reflexes, muscular atrophy, and gradually increasing contractures. Pathologically, the disease is characterized by chromatolysis, neuronophagia and reduction in the number of the large motor neurons in the motor nuclei of the fifth to twelfth cranial nerves and in the anterior horns of the spinal cord. Similar changes in and preference for these large motor neurons is seen in the acute stage of infection with certain small ribonucleic acid (RNA) viruses, such as poliomyelitis and mengoencephalomyelitis (3, 4). Because of this similarity, RNA metabolism in some of the neurons affected by infantile spinal muscular atrophy has been studied in search of a specific biochemical defect. The technic involved the intracisternal injection of Uridine-5H3, a specific precursor in the synthesis of RNA (5), and study of the in vivo uptake of this tracer by radioautography post mortem.